bluuebunny/crossref_metadata_2025 huggingface dataset:
FODMAP modulation as a dietary therapy for IBS: Scientific and market perspective
Authors: Ispiryan Lilit , Zannini Emanuele , Arendt Elke K.
Published: February 2022

A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is a promising therapeutic approach to reduce gastrointestinal symptoms associated with irritable bowel syndrome (IBS). However, a shift toward a more sustainable, healthy diet with higher inclusion of whole‐grain cereals (i.e., wheat, rye, barley) and pulses, naturally rich in FODMAPs, poses a severe challenge for susceptible individuals. Dietary restriction of fermentable carbohydrates (commonly called the “low FODMAP diet”) has received significant consideration. Hence, the development of functional low FODMAP products is emerging in food science and the food industry. In this review, we evaluate the most promising yet neglected (bio)‐technological strategies adopted for modulating the FODMAP contents in complex food systems and the extent of their uptake in the global food market. We extensively investigated the global low FODMAP market, contrasted with the status quo in food science and discussed the key principles and concomitant challenges of targeted FODMAP reduction strategies. Powerful tools are available which are based either on the use of ingredients where FODMAPs have been physically removed (e.g., by membrane filtration) or biotechnologically reduced during the food processing, mediated by added enzymes, microbial enzymes during a fermentation process, and seed endogenous enzymes. However, <10% of the small market of functional products with a low FODMAP claim (total ∼800 products) used any of the targeted FODMAP reduction techniques. The global market is currently dominated by gluten‐free products, which are naturally low in FODMAPs and characterized by inferior sensory attributes.
Effects of Climate, Basin Characteristics, and High‐Capacity Wells on Baseflow in the State of Wisconsin, United States
Authors: Borchardt Susan , Choi Woonsup , Choi Jinmu
Published: February 2022

When it comes to water resources management, it is critical to understand the factors that affect baseflow processes. Declines in baseflow due to increased use of the groundwater from unconfined aquifers is well documented, but that is not the case for confined aquifers. Furthermore, since the groundwater basin size and shape can be different than the surface water basin, the use of the surface basin to determine well withdrawal rates can affect baseflow and be problematic. This study used the variables determined to be related to baseflow variability (precipitation, temperature, drainage class, available storage, land use, and slope) and the withdrawal rates of wells located within the study basins to create regression models for the state of Wisconsin, United States. We find that: (1) precipitation and temperature variable are significant in explaining the temporal variability of baseflow, whereas land cover variables are important when the temporal variability is not considered; (2) evaporation and soil drainage are important in basins over unconfined aquifers, whereas precipitation the most significant over confined aquifers; (3) whether to use surface water or groundwater divides to delineate basins matters in particular conditions, and (4) groundwater withdrawal rates do not significantly affect baseflow when using statistical analysis. Therefore, analyzing baseflow should be supplemented by a process‐based model for the effects of groundwater withdrawals.
Cardiac dysfunction and mortality in critically ill patients with COVID‐19: A Swedish multicentre observational study
Authors: Holmqvist Jacob , Beck‐Friis Josefine , Jensen Carl , Dalla Keti , Mårdstam Simon , Christensen Jens , Nordén Nina , Widing Hannes , Rosén‐Wetterholm Elin , Cavefors Oscar , Yilmaz Aylin , Cronhjort Maria , Redfors Björn , Oras Jonatan
Published: February 2022

Background

The prevalence and importance of cardiac dysfunction in critically ill patients with COVID‐19 in Sweden is not yet established. The aim of the study was to assess the prevalence of cardiac dysfunction and elevated pulmonary artery pressure (PAP), and its influence on mortality in patients with COVID‐19 in intensive care in Sweden.

Methods

This was a multicentre observational study performed in five intensive care units (ICUs) in Sweden. Patients admitted to participating ICU with COVID‐19 were examined with echocardiography within 72 h from admission and again after 4 to 7 days. Cardiac dysfunction was defined as left ventricular (LV) dysfunction (ejection fraction <50% and/or regional hypokinesia) or right ventricular (RV) dysfunction (defined as TAPSE <17 mm or visually assessed moderate/severe RV dysfunction).

Results

We included 132 patients, of whom 127 (96%) were intubated. Cardiac dysfunction was found in 42 (32%) patients. Most patients had cardiac dysfunction at the first assessment (n = 35) while a few developed cardiac dysfunction later (n = 7) and some changed type of dysfunction (n = 3). LV dysfunction was found in 21 and RV dysfunction in 19 patients, while 5 patients had combined dysfunction. Elevated PAP was found in 34 patients (26%) and was more common in patients with RV dysfunction. RV dysfunction and elevated PAP were independently associated with an increased risk of death (OR 3.98, p = .013 and OR 3.88, p = .007, respectively).

Conclusions

Cardiac dysfunction occurs commonly in critically ill patients with COVID‐19 in Sweden. RV dysfunction and elevated PAP are associated with an increased risk of death.
CEO organizational identification and corporate innovation investment
Authors: Du Dongying , Tang Xiaojian , Wang Huaiming , Zhang Joseph H. , Tsui Stephanie , Lin Dongjie
Published: February 2022

Identity theory in economics reveals that organisational identification motivates managers to take actions that are strongly aligned with firm interests. Nevertheless, organisational identification may also play a role in personal incentives. Leveraging the availability of CEO organisational identification data from the national internal control survey of listed firms in China, we document a positive impact of CEO organisational identification on corporate innovation. We also find that the positive impact is more pronounced for firms whose CEOs own shares, that are followed by more financial analysts, and that have higher institutional ownership. Additional analyses suggest that the interaction between CEO organisational identification and corporate innovation investment significantly enhances firm value. Overall, our study shows that CEO organisational identification is a non‐trivial driver of firm innovation and growth.
Elevated transferrin saturation in individuals with alcohol use disorder: Association with HFE polymorphism and alcohol withdrawal severity
Authors: Kroll Danielle S. , McPherson Katherine L. , Manza Peter , Schwandt Melanie L. , Shen Pei‐Hong , Goldman David , Diazgranados Nancy , Wang Gene‐Jack , Wiers Corinde E. , Volkow Nora D.
Published: February 2022

Iron loading has been consistently reported in those with alcohol use disorder (AUD), but its effect on the clinical course of the disease is not yet fully understood. Here, we conducted a cohort study to examine whether peripheral iron measures, genetic variation in HFE rs1799945 and their interaction differed between 594 inpatient participants with alcohol use disorder (AUD) undergoing detoxification and 472 healthy controls (HC). We also assessed whether HFE rs1799945 was associated with elevated peripheral iron and can serve as a predictor of withdrawal severity. AUD patients showed significantly higher serum transferrin saturation than HC. Within the AUD group, transferrin saturation significantly predicted withdrawal symptoms (CIWA‐Ar) and cumulative dose of benzodiazepine treatment during the first week of detoxification, which is an indicator of withdrawal severity. HFE rs1799945 minor allele carriers showed elevated transferrin saturation compared to non‐carriers, both in AUD and healthy controls. Exploratory analyses indicated that, within the AUD cohort, HFE rs1799945 predicted CIWA withdrawal scores, and this relationship was significantly mediated by transferrin saturation. We provide evidence that serum transferrin saturation predicts alcohol withdrawal severity in AUD. Moreover, our findings replicated previous studies on elevated serum transferrin saturation in AUD and an involvement of HFE rs1799945 in serum transferrin saturation levels in both AUD and healthy controls. Future studies may use transferrin saturation measures as predictors for treatment or potentially treat iron overload to ameliorate withdrawal symptoms.
Identifying and managing adverse drug reactions: Qualitative analysis of patient reports to the UK yellow card scheme
Authors: O' Donovan Bernadine , Rodgers Ruth M. , Cox Anthony R. , Krska Janet
Published: February 2022

Introduction

Adverse drug reactions (ADRs) can have significant negative impact on peoples' daily lives, with physical, economic, social and/or psychological effects. Patient reporting of ADRs has been facilitated by pharmacovigilance systems across Europe. However, capturing data on patients' experiences of ADRs has proved challenging. Existing patient reports to the UK Yellow Card Scheme contain free‐text comments which could be useful sources of information.

Objectives

To investigate patients' experiences of ADRs and their impact on patients as described in free‐text data within patient Yellow Card (YC) reports submitted to the Medicines and Healthcare products Regulatory Agency.

Methods

A qualitative review of narrative texts was conducted on free‐text data from 2255 patient YC reports from July to December 2015.

Results

Three key narrative themes emerged from analysis of the free‐text data in 2255 reports: (1) identification of ADRs, (2) severity and impact of ADRs, and (3) management of ADRs. Temporal associations were the most common method of identification followed by differential diagnoses and confirmation with information sources such as healthcare professionals (HCPs). A combination of explicit and implicit impacts were described: physical, psychological, economic and social effects often persisted and caused serious disruption to many patients' lives. A range of strategies were used to manage ADRs, including consultation with HCPs, stopping/reducing the medicine or taking medicines to alleviate symptoms.

Conclusion

Free‐text data from YC reports has been an underutilised resource to date, but this research has confirmed its potential value to pharmacovigilance and medication safety research.
Urological General Medical Council (GMC) fitness to practice complaints in the UK: an analysis over the last 14 years (2007–2021) based on trends, ethnicity and outcomes
Authors: Lane Jenni , Somani Bhaskar K.
Published: February 2022

Objectives

To present the number and outcomes of urological referrals to the General Medical Council (GMC) and provide a breakdown of the doctors' demographics.

Methods

Data were requested and collected from the GMC under the Freedom of Information Act 2000 for all complaints about urologists between 2007 and 2021 (14‐year period).

Results

Between 2007 and 2021 a total of 635 urologists were referred to the GMC, totalling 734 referrals (1.15 referrals/doctor). Of these, 50% (364) were closed following a provisional enquiry (PE; 1 month) and another 43% were investigated but no action was taken. Action was taken for only 7% of urologists (49); these urologists were given advice, required to do extra training, suspended from practice, or erased from the medical register. Compared to the current urology workforce, a marginally higher proportion of those referred were international medical graduates or from diverse backgrounds.

Conclusion

For urologists unfairly referred to the GMC it is reassuring to know that half of cases are closed at a PE. Of those investigated, only 7% of urologists were given sactions, suspension or given extra training. Reassuringly, our data demonstrate a robust process of GMC investigation, with most doctors going back into work following suitable complaints and, over the last 14 years, only nine urologists received sanctions, two of whom were erased from the medical register. There were only marginal differences when comparing our data to the current urologist population with regard to race and location of primary medical qualification. Conversely, the male‐to‐female split was more heavily weighted towards males being referred to the GMC.
Successful diagnosis of attention deficit hyperactivity disorder in later life of an adult with intellectual disability: A case report
Authors: Raji Oyepeju , Javaid Shafaq
Published: February 2022

Background

Diagnosing and managing attention deficit hyperactivity disorder in adults with intellectual disabilities is currently largely based on findings from assessment and treatment in children or adults without intellectual disabilities. Current evidence suggests that individuals with intellectual disabilities are more likely to have attention deficit hyperactivity disorder compared to those without intellectual disabilities, but more research is needed. There is increasing knowledge of diagnosing and treating attention deficit hyperactivity disorder in people with intellectual disabilities with published guidance on delivering care based on good evidence. More is needed so that clinicians do not have to depend on the evidence from those who do not have intellectual disabilities.

Method

To write this report, we reviewed a female in her 50s with mild intellectual disability who has been known to general and specialist intellectual disability mental health services for at least 20 years over many episodes of care. We assessed her clinically and using the Diagnostic Interview for attention deficit hyperactivity disorder in Adults with intellectual disabilities to make a diagnosis of attention deficit hyperactivity disorder. We call her Mary, which is not her real name.

Findings

Mary has had many diagnoses however, we found that her neurodevelopmental disorders of attention deficit hyperactivity disorder and we believe, autism were missed which led to a complex presentation of behavioural and mental symptoms; and diagnostic and management challenges. Mary was receiving combinations of medications known as antipsychotics, antidepressants, hypnotics and mood stabilisers to high doses. She was able to stop them all successfully over 12–18 months before being diagnosed with attention deficit hyperactivity disorder. Once diagnosed with attention deficit hyperactivity disorder, Mary rapidly responded to a long acting stimulant as recommended by the National Institute for Health and Care Excellence and this has significantly improved her quality of life.

Conclusion

Attention deficit hyperactivity disorder in people with intellectual disabilities is often missed and inadequately managed, despite having highly effective and specific treatment strategies. Making the diagnoses of attention deficit hyperactivity disorder and intellectual disabilities is important as individuals with both together have worse outcomes. Therefore, effective treatment of attention deficit hyperactivity disorder in individuals with intellectual disabilities is critical.
A Survey of Tasks and Visualizations in Multiverse Analysis Reports
Authors: Hall Brian D. , Liu Yang , Jansen Yvonne , Dragicevic Pierre , Chevalier Fanny , Kay Matthew
Published: February 2022

Analysing data from experiments is a complex, multi‐step process, often with multiple defensible choices available at each step. While analysts often report a single analysis without documenting how it was chosen, this can cause serious transparency and methodological issues. To make the sensitivity of analysis results to analytical choices transparent, some statisticians and methodologists advocate the use of ‘multiverse analysis’: reporting the full range of outcomes that result from all combinations of defensible analytic choices. Summarizing this combinatorial explosion of statistical results presents unique challenges; several approaches to visualizing the output of multiverse analyses have been proposed across a variety of fields (e.g. psychology, statistics, economics, neuroscience). In this article, we (1) introduce a consistent conceptual framework and terminology for multiverse analyses that can be applied across fields; (2) identify the tasks researchers try to accomplish when visualizing multiverse analyses and (3) classify multiverse visualizations into ‘archetypes’, assessing how well each archetype supports each task. Our work sets a foundation for subsequent research on developing visualization tools and techniques to support multiverse analysis and its reporting.
Skin tests in the work‐up of cutaneous adverse drug reactions: A review and update
Authors: Barbaud Annick , Castagna Julie , Soria Angèle
Published: February 2022

Skin tests, including patch tests (PTs), prick tests, and intradermal tests (IDTs), are useful in identifying the culprits of cutaneous adverse drug reactions (CADRs), and determining safer, alternative drugs. PTs have a low sensitivity but are valuable in investigating maculopapular exanthema (MPE), as well as severe CADR, including toxic epidermal necrolysis (TEN), Stevens‐Johnson syndrome (SJS), and in particular, acute generalized exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS). To ensure their specificity, at least 10 control tests should be performed. Prick tests are mainly used in the evaluation of immediate‐type hypersensitivity and can be performed with all drugs, except opiates. IDTs can be used to explore immediate and delayed‐type hypersensitivity, if an injectable form of the drug exists. Except for SJS/TEN, IDTs should be performed by injecting 0.02 mL of the drug. We here provide a practical, up‐to‐date review on the use of these skin tests in the work‐up of CADRs. Numerous negative controls for drug PTs, as well as criteria for the immediate and delayed positivity of prick tests and IDT, are included. It should be emphasized that a negative result never excludes the potential responsibility of a drug in a CADR.
PIPS: A Parallel Planning Model of Sentence Production
Authors: Brehm Laurel , Cho Pyeong Whan , Smolensky Paul , Goldrick Matthew A.
Published: February 2022

Subject–verb agreement errors are common in sentence production. Many studies have used experimental paradigms targeting the production of subject–verb agreement from a sentence preamble (The key to the cabinets) and eliciting verb errors (… *were shiny). Through reanalysis of previous data (50 experiments; 102,369 observations), we show that this paradigm also results in many errors in preamble repetition, particularly of local noun number (The key to the *cabinet). We explore the mechanisms of both errors in parallelism in producing syntax (PIPS), a model in the Gradient Symbolic Computation framework. PIPS models sentence production using a continuous‐state stochastic dynamical system that optimizes grammatical constraints (shaped by previous experience) over vector representations of symbolic structures. At intermediate stages in the computation, grammatical constraints allow multiple competing parses to be partially activated, resulting in stable but transient conjunctive blend states. In the context of the preamble completion task, memory constraints reduce the strength of the target structure, allowing for co‐activation of non‐target parses where the local noun controls the verb (notional agreement and locally agreeing relative clauses) and non‐target parses that include structural constituents with contrasting number specifications (e.g., plural instead of singular local noun). Simulations of the preamble completion task reveal that these partially activated non‐target parses, as well the need to balance accurate encoding of lexical and syntactic aspects of the prompt, result in errors. In other words: Because sentence processing is embedded in a processor with finite memory and prior experience with production, interference from non‐target production plans causes errors.
The Role of Stimulus‐Specific Perceptual Fluency in Statistical Learning
Authors: Perfors Andrew , Kidd Evan
Published: February 2022

Humans have the ability to learn surprisingly complicated statistical information in a variety of modalities and situations, often based on relatively little input. These statistical learning (SL) skills appear to underlie many kinds of learning, but despite their ubiquity, we still do not fully understand precisely what SL is and what individual differences on SL tasks reflect. Here, we present experimental work suggesting that at least some individual differences arise from stimulus‐specific variation in perceptual fluency: the ability to rapidly or efficiently code and remember the stimuli that SL occurs over. Experiment 1 demonstrates that participants show improved SL when the stimuli are simple and familiar; Experiment 2 shows that this improvement is not evident for simple but unfamiliar stimuli; and Experiment 3 shows that for the same stimuli (Chinese characters), SL is higher for people who are familiar with them (Chinese speakers) than those who are not (English speakers matched on age and education level). Overall, our findings indicate that performance on a standard SL task varies substantially within the same (visual) modality as a function of whether the stimuli involved are familiar or not, independent of stimulus complexity. Moreover, test–retest correlations of performance in an SL task using stimuli of the same level of familiarity (but distinct items) are stronger than correlations across the same task with stimuli of different levels of familiarity. Finally, we demonstrate that SL performance is predicted by an independent measure of stimulus‐specific perceptual fluency that contains no SL component at all. Our results suggest that a key component of SL performance may be related to stimulus‐specific processing and familiarity.
When the “Tabula” is Anything but “Rasa:” What Determines Performance in the Auditory Statistical Learning Task?
Authors: Elazar Amit , Alhama Raquel G. , Bogaerts Louisa , Siegelman Noam , Baus Cristina , Frost Ram
Published: February 2022

How does prior linguistic knowledge modulate learning in verbal auditory statistical learning (SL) tasks? Here, we address this question by assessing to what extent the frequency of syllabic co‐occurrences in the learners’ native language determines SL performance. We computed the frequency of co‐occurrences of syllables in spoken Spanish through a transliterated corpus, and used this measure to construct two artificial familiarization streams. One stream was constructed by embedding pseudowords with high co‐occurrence frequency in Spanish (“Spanish‐like” condition), the other by embedding pseudowords with low co‐occurrence frequency (“Spanish‐unlike” condition). Native Spanish‐speaking participants listened to one of the two streams, and were tested in an old/new identification task to examine their ability to discriminate the embedded pseudowords from foils. Our results show that performance in the verbal auditory SL (ASL) task was significantly influenced by the frequency of syllabic co‐occurrences in Spanish: When the embedded pseudowords were more “Spanish‐like,” participants were better able to identify them as part of the stream. These findings demonstrate that learners’ task performance in verbal ASL tasks changes as a function of the artificial language's similarity to their native language, and highlight how linguistic prior knowledge biases the learning of regularities.
Knowledge in Sight: Toddlers Plan Efficient Epistemic Actions by Anticipating Learning Gains
Authors: Aguirre Marie , Brun Mélanie , Couderc Auriane , Reboul Anne , Senez Philomène , Mascaro Olivier
Published: February 2022

Anticipating the learning consequences of actions is crucial to plan efficient information seeking. Such a capacity is needed for learners to determine which actions are most likely to result in learning. Here, we tested the early ontogeny of the human capacity to anticipate the amount of learning gained from seeing. In study 1, we tested infants’ capacity to anticipate the availability of sight. Fourteen‐month‐old infants (N = 72) were invited to search for a toy hidden inside a container. The participants were faster to attempt at opening a shutter when this action allowed them to see inside the container. Moreover, this effect was specifically observed when seeing inside the container was potentially useful to the participants’ goals. Thus, infants anticipated the availability of sight, and they calibrated their information‐seeking behaviors accordingly. In studies 2 and 3, we tested toddlers’ capacity to anticipate whether data would be cognitively useful for their goals. Two‐and‐a‐half‐year‐olds (N = 72) had to locate a target character hidden among distractors. The participants flipped the characters more often, and were comparatively faster to initiate this action when it yielded access to visual data allowing them to locate the target. Thus, toddlers planned their information‐seeking behaviors by anticipating the cognitive utility of sight. In contrast, toddlers did not calibrate their behaviors to the cognitive usefulness of auditory data. These results suggest that cognitive models of learning guide toddlers’ search for information. The early developmental onset of the capacity to anticipate future learning gains is crucial for active learning.
Definition, prevalence, and clinical significance of mitral annular disjunction in different patient cohorts: A systematic review
Authors: Bennett Sadie , Tafuro Jacopo , Duckett Simon , Appaji Anik , Khan Jamal Nasir , Heatlie Grant , Cubukcu Arzu , Kwok Chun Shing
Published: February 2022

Background

Mitral annular disjunction (MAD) is a structural abnormality involving a distinct separation of the left atrium/mitral valve annulus and myocardium continuum. The literature around MAD has increased over recent years, thus we sought to review the current data on the definition, prevalence, and clinical outcomes of MAD.

Methods

A search of MEDLINE and EMBASE was conducted to identify studies which evaluated MAD in any patient cohort. The study results were synthesized narratively.

Results

A total of 12 studies were included with 3925 patients (average age 62 years, 63% male). The pooled prevalence of MAD in patients with mitral valve prolapse and/or Barlow's disease was 30.1%. In a general population, MAD prevalence was 8.7%. The definition of MAD was not consistent across all studies. In terms of clinical outcomes, only one study reported MAD to be associated with ventricular arrhythmias.

Conclusions

MAD is an increasingly recognized finding amongst patients undergoing cardiac imaging. This review highlights the need for agreed definitions for clinically significant MAD and how identified MAD should be managed. At present, there is insufficient evidence that MAD is associated adverse clinical outcomes.
Incidence and socioeconomic factors in older adults with acute myeloid leukaemia: Real‐world outcomes from a population‐based cohort
Authors: Stubbins Ryan J. , Stamenkovic Maria , Roy Claudie , Rodrigo Judith , Chung Shanee , Kuchenbauer Florian C. , Hay Kevin A. , White Jennifer , Abou Mourad Yasser , Power Maryse M. , Narayanan Sujaatha , Forrest Donna L. , Toze Cynthia L. , Sutherland Heather J. , Nantel Stephen H. , Nevill Thomas J. , Karsan Aly , Song Kevin W. , Sanford David S.
Published: February 2022

Objectives

Acute myeloid leukaemia (AML) is a disease of older adults, who are vulnerable to socio‐economic factors. We determined AML incidence in older adults and the impact of socio‐economic factors on outcomes.

Methods

We included 3024 AML patients (1996–2016) identified from a population‐based registry.

Results

AML incidence in patients ≥60 years increased from 11.01 (2001–2005) to 12.76 (2011–2016) per 100 000 population. Among 879 patients ≥60 years in recent eras (2010–2016), rural residents (<100 000 population) were less likely to be assessed by a leukaemia specialist (39% rural, 47% urban, p = .032); no difference was seen for lower (43%, quintile 1–3) vs. higher (47%, quintile 4–5) incomes (p = .235). Similar numbers received induction chemotherapy between residence (16% rural, 18% urban, p = .578) and incomes (17% lower, 17% high, p = 1.0). Differences between incomes were seen for hypomethylating agent treatment (14% low, 20% high, p = .041); this was not seen for residence (13% rural, 18% urban, p = .092). Among non‐adverse karyotype patients ≥70 years, 2‐year overall survival was worse for rural (5% rural, 12% urban, p = .006) and lower income (6% low, 15% high, p = .017) patients.

Conclusions

AML incidence in older adults is increasing, and outcomes are worse for older rural and low‐income residents; these patients face treatment barriers.
Antibodies gone bad – the molecular mechanism of light chain amyloidosis
Authors: Absmeier Ramona M. , Rottenaicher Georg J. , Svilenov Hristo L. , Kazman Pamina , Buchner Johannes
Published: February 2022

Light chain amyloidosis (AL) is a systemic disease in which abnormally proliferating plasma cells secrete large amounts of mutated antibody light chains (LCs) that eventually form fibrils. The fibrils are deposited in various organs, most often in the heart and kidney, and impair their function. The prognosis for patients diagnosed with AL is generally poor. The disease is set apart from other amyloidoses by the huge number of patient‐specific mutations in the disease‐causing and fibril‐forming protein. The molecular mechanisms that drive the aggregation of mutated LCs into fibrils have been enigmatic, which hindered the development of efficient diagnostics and therapies. In this review, we summarize our current knowledge on AL amyloidosis and discuss open issues.
Interplays between changing biophysical and social dynamics under climate change: Implications for limits to sustainable adaptation in food systems
Authors: Bezner Kerr Rachel , Naess Lars Otto , Allen‐O’Neil Bridget , Totin Edmond , Nyantakyi‐Frimpong Hanson , Risvoll Camilla , Rivera Ferre Marta G. , López‐i‐Gelats Feliu , Eriksen Siri
Published: February 2022

Climate change scenarios have significant implications for the livelihoods and food security of particular groups in society and will necessitate a range of adaptation actions. While there is a significant literature on the social as well as biophysical factors and limits to adaptation, less is known about the interactions between these, and what such interactions mean for the prospects of achieving sustainable and resilient food systems. This paper is an attempt at addressing this gap by examining changing biophysical and social factors, with specific consideration of vulnerable groups, across four case studies (Ghana, Malawi, Norway and Spain). In each case, future climate change scenarios and associated biophysical limits are mapped onto four key social factors that drive vulnerability and mediate adaptation, namely, scale, history, power and politics, and social differentiation. We then consider what the interaction between biophysical limits and socio‐political dynamics means for the options for and limits to future adaptation, and how climate may interact with, and reshape, socio‐political elements. We find that biophysical limits and socio‐political factors do not operate in isolation, but interact, with dynamic relationships determining the ‘space’ or set of options for sustainable adaptation. By connecting the perspectives of biophysical and social factors, the study illuminates the risks of unanticipated outcomes that result from the disregard of local contexts in the implementation of adaptation measures. We conclude that a framework focusing on the space for sustainable adaptation conditioned by biophysical and social factors, and their interactions, can help provide evidence on what does and does not constitute sustainable adaptation, and help to counter unhelpful narratives of climate change as a sole or dominant cause of challenges in food systems.
Living with a genetic, undiagnosed or rare disease: A longitudinal journalling study through the COVID‐19 pandemic
Authors: Byun Malia , Feller Hollie , Ferrie Monica , Best Stephanie
Published: February 2022

Introduction

COVID‐19 changed the way we lived with uncertainty from the outset as the pandemic impacted every aspect of our lives from well‐being, socializing to accessing healthcare. For people in vulnerable populations, such as those with genetic, undiagnosed and rare disorders, the experience was heightened.

Aim

The aim of this study was to identify how the rapidly changing COVID‐19 environment impacted the lives of the Genetic, Undiagnosed and Rare Disease community.

Methods

From June 2020 to May 2021, we collected monthly open‐ended journals from people living in Australia with genetic, undiagnosed and rare disorders. Data analysis was deductive, using the Resilience Scale for Adults, and inductive using thematic analysis.

Results

We recruited 29 people (average of n = 9.7 submissions each month). Responses changed over the year, with initial journals focusing on the importance of developing new structures for day‐to‐day lives, while later journals started to focus on mental well‐being. Throughout the project, participants reported challenges in accessing health and social care that was compounded by fear and concern over being exposed to the virus. Later journals highlight inconsistent messaging for vaccinations for this vulnerable community.

Discussion/Conclusion

In parallel with the waves of the COVID‐19 pandemic, there need to be waves of targeted support for vulnerable communities. The first support wave needs to focus on facilitating the identification of new frameworks to structure day‐to‐day lives. A later second wave needs to focus on mental well‐being and coping with isolation, while consistent communication relating to health and social care throughout was essential.

Patient/Public Contribution

This study was co‐designed, co‐led and analysed with a patient support network.
CDX2 expression in malignant peripheral nerve sheath tumour: a potential diagnostic pitfall associated with PRC2 inactivation
Authors: Odeyemi Olumide O , Ozawa Michael G , Charville Gregory W
Published: February 2022

Aims

Malignant peripheral nerve sheath tumour (MPNST) is a soft tissue sarcoma that exhibits features of Schwann cell differentiation. Heterologous, often mesenchymal‐type differentiation occurs in a subset of MPNST, while glandular morphology also is encountered in rare cases. We observed in MPNST unanticipated expression of CDX2, a transcription factor that regulates intestinal epithelial differentiation, and aimed to further characterize this phenomenon.

Methods/Results

Expression of CDX2 was assessed by immunohistochemistry in a total of 32 high‐grade MPNSTs lacking morphological evidence of epithelial differentiation, including twelve tumours (38%) that developed in the setting of neurofibromatosis and four (13%) in the setting of prior radiation therapy. CDX2 was expressed by 14 of 32 MPNSTs (44%), wherein immunoreactivity, varying from weak to strong, was present in 2–95% of neoplastic spindle cells (median 10%, mean 23%). Notably, CDX2 expression was limited to tumours with PRC2 inactivation (22/32; 69%), as evidenced immunohistochemically by diffuse loss of trimethylated histone H3K27. Analysing publicly available RNA‐sequencing data from twelve MPNST cell lines, two of which are clonally related, we observed CDX2 expression in all six PRC2‐inactivated cell lines, while CDX2 expression was negligible in six cell lines with intact PRC2, amounting to a 58‐fold increase in CDX2 expression on average with PRC2 inactivation.

Conclusions

CDX2 is expressed in a subset of MPNSTs, even in the absence of morphological evidence of epithelial differentiation. CDX2 expression in MPNST is strongly associated with underlying PRC2 inactivation.
Substitution of antioxidant Si by andalusite fine powder in Al2O3‐SiC‐C castables
Authors: Fu Yunhe , Niu Zheng , Mu Yuandong , Hao Zhanhong , Wang Qingfeng , Parr Chris , Ye Guotian
Published: February 2022

Our previous research showed that the addition of andalusite aggregates can enhance the oxidation resistance of Al2O3‐SiC‐C castables; this is attributed to the transformation of andalusite into a silica‐rich glass phase that blocks pores. Theoretically, andalusite with a smaller particle size would achieve a higher extent of conversion and generate more silica‐rich glass, which would be more conducive to blocking pores. Therefore, this study evaluates the influence of andalusite fine powder on the oxidation resistance of Al2O3‐SiC‐C castables containing a reduced amount of Si antioxidant. The results show that introducing a small amount of andalusite fine powder endows the Al2O3‐SiC‐C castables with significant oxidation resistance so that the traditional addition of Si metal as an antioxidant can be substantially reduced or even completely eliminated. Meanwhile, the thermal shock stability and strength of the castables were also enhanced.
Using more effective instructional verbs to elevate auditors' professional scepticism
Authors: Stepankova Sarka , Harding Noel , Mayorga Diane M. , Trotman Ken T.
Published: February 2022

We investigate whether using different instructional verbs to codify requirements in auditing standards, and to direct auditors in meeting those requirements, impacts the level of professional scepticism reflected in auditor judgments and the evidence auditors intend to collect. In an experiment, with practicing auditors serving as participants, we test whether directing auditors with higher order instructional verbs (e.g., consider and evaluate), rather than with lower order instructional verbs that are currently employed (e.g., review and identify), elevates auditors' professional scepticism. We investigate the level of professional scepticism reflected in two auditor judgments and the evidence that auditors intend to collect. Although we find that different instructional verbs did not have an effect on the level of scepticism reflected in auditor judgments, the use of higher order instructional verbs did elevate the level of scepticism reflected in the evidence auditors intend to collect. Our finding has important implications for the way in which auditing standards are drafted and the way in which auditors are guided by written instructions.
Comparison of fit accuracy between conventional and CAD/CAM‐fabricated band–loop space maintainers
Authors: Tokuc Muge , Yilmaz Hakan
Published: February 2022

Aim

The aim of this in vitro study was to evaluate the band fit of metallic band–loop space maintainers fabricated by conventional and 3D printing technologies for clinical applications.

Design

Sixteen digital intraoral impressions were selected, and resin models were printed with a 3D printer. Forty band–loop space maintainers were fabricated (20 each for both the conventional and digital groups). To evaluate the band fit of conventional and CAD/CAM‐fabricated space maintainers, cement space was visualized with low‐viscosity condensation silicone material on resin models. Digital evaluation was carried out using dual scan method by superimposing two scans of resin models covered with or without a silicone layer on the abutment tooth. The mean quadratic deviation (root mean square, RMS) was calculated. The RMS values between the groups were evaluated with Student's t test. Statistical significance was set at p < .05.

Results

No statistical significance was found between the conventional and digital groups (p = .56).

Conclusions

Within the limitations of this study, the band fit of conventional and CAD/CAM‐fabricated space maintainers had no difference. Future research into CAD/CAM‐fabricated appliances from different perspectives such as fracture strength and patient comfort is warranted.
Experimental protocols for the assessment of redox thermodynamics of nonstoichiometric oxides: A case study of YMnO3‐δ
Authors: Qian Xin , Haile Sossina M. , Davenport Timothy C. , Mastronardo Emanuela
Published: February 2022

The thermodynamics of reduction in variable valence oxides are important in a vast number of fields in which point defects, and in particular oxygen vacancies, control material functionality. Here, we present, by way of an example measurement of the material YMnO3‐δ, for which the vacancy formation energy has not been previously reported, best practices for material characterization. Sample mass is recorded by thermogravimetric analysis at temperatures from 600 to 1500°C under five different gas atmospheres, with oxygen partial pressure ranging from 0.081 to 7.66 × 10–5 atm. Because YMnO3‐δ displays relatively small nonstoichiometry, less than 0.09, over the range of conditions examined, a large sample was required to record the modest mass changes. In the more oxidizing conditions, equilibrium behavior was recorded using a finite heating rate of 10°C min–1. In the more reducing conditions, absolute mass changes with temperature were large such that the evolved oxygen increased the oxygen partial pressure in the sample vicinity, precluding equilibration under finite heating. Accordingly, a temperature‐stepped protocol with long isothermal holds was employed. Analysis of the results from these stepped measurements required interpolation, which was carried out on the ln(δ) versus 1/T plane. In the nonpolar, centrosymmetric phase (P63/mcm and δ ≥ 0.016), the enthalpy of reduction was found to be 304 ± 4 kJ (mol‐O)–1, as averaged over the δ range 0.020–0.035. While YMnO3‐δ is known to incorporate oxygen excess in its ambient temperature, polar phase (P63cm), the conditions leading to such behavior were not included in this study.
Physical–biological interactions underlying the connectivity patterns of coral‐dependent fishes around the Arabian Peninsula
Authors: Torquato Felipe , Møller Peter R.
Published: February 2022

Aim

Distribution patterns of lineages alone do not explain the processes underlying phylogenetic differentiation in fishes observed around the Arabian Peninsula, whose hypotheses traditionally rely on (i) Pleistocene vicariance events, (ii) successive bottlenecks, (iii) recent founder effects (iv) and large spatial gradients in physical conditions. In this study, we test the hypothesis that phylogeographical patterns of coral‐dependent fish species inhabiting the peninsula may be driven by a combination of ocean circulation, larval behaviour and seascape features.

Location

Arabian Peninsula.

Taxa

Coral reef fish.

Methods

A biophysical modelling system that relies on stochastic Lagrangian framework and Individual‐Based Model was used to simulate larval dispersal through three putative barriers, by tracking three‐dimensional movements of virtual particles in ocean circulation scenarios. We explored the range of dispersal capabilities across reef fish species by creating 72 hypothetical strategies, each representing a unique combination of five biological traits, namely pelagic larval duration, spawning periodicity, mortality rate, reproductive output and vertical migration.

Results

The strength of the barriers was highly variable as a function of all biological traits (except reproductive output) and indicated high asymmetry of connectivity, and hence gene flow, between adjacent areas. In addition, direction and distance travelled by the virtual larvae varied according to both the geographical position of releasing site and biannual monsoonal winds. On average, larvae released during the summer exhibited a higher potential for dispersal than larvae released during the winter.

Main conclusions

Our biophysical models showed that in the Arabian Peninsula, the combination of hydrodynamic, seascape features and larval traits likely affects the distribution of genetic lineages due to the interruption, reduction or asymmetry of larval movements through the putative barriers.
A codesigned fit‐for‐purpose implementation framework for aged care
Authors: Meyer Claudia , Ogrin Rajna , Golenko Xanthe , Cyarto Elizabeth , Paine Kath , Walsh Willeke , Hutchinson Alison , Lowthian Judy
Published: February 2022

Rationale, Aims and Objectives

The field of implementation science is critical for embedding research evidence into healthcare practice, benefiting individuals, organizations, governments, and the broader community. Implementation science is messy and complex, underpinned by many theories and frameworks. Efficacious interventions for older people with multiple comorbidities exist, yet many lack effectiveness evaluation relevant to pragmatic implementation within aged care practice. This article outlines the conceptualization and development of an Implementation Framework for Aged Care (IFAC), fit‐for‐purpose for an aged care organization, Bolton Clarke, intent on embedding evidence into practice.

Method

A four‐stage process was adopted to (1) explore context and relevant literature to conceptualize the IFAC; (2) identify key elements for a draft IFAC; (3) expand elements and refine the draft in consultation with experts and (4) apply the IFAC to three existing projects, identifying key learnings. A checklist to operationalize the IFAC was then developed.

Results

The IFAC is grounded in codesign principles and encapsulated by the implementation context, from a social, cultural and political perspective. The IFAC addresses the questions of (1) why do we need to change?; (2) what do we know?; (3) who will benefit?; (4) who will make the change?; (5) what strategies will be used?; and (6) what difference are we making? Three pilot projects: early adoption of a Wellness and Reablement approach; a care worker and virtual physiotherapist‐led program to prevent falls; and a therapeutic horticulture program for residential communities, highlight learnings of applying the IFAC in practice.

Conclusion

This fit‐for‐purpose IFAC was developed for a proactive and responsive aged care provider. The simplicity of the six‐question IFAC is underpinned by substantial theoretical perspectives for its elements and their connections. This complexity is then consolidated into an 18‐question checklist to operationalize the IFAC, necessary to advance the translation of evidence into clinical practice.