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The establishment of a peripheral ECMO circuit can lead to significant arterial and venous complications in 10–30% of patients. Vascular complications, particularly acute limb ischemia, are associated with worsening overall outcomes. Limb ischemia occurs significantly more frequently in the early stages of VA ECMO than in VV ECMO. Mechanisms of limb ischemia include arterial obstruction, cannulation injury, loss of pulsatile flow, thromboembolism, venous stasis from compressive obstruction with large venous cannulas, and systemic vasoconstriction due to shock and pharmacologic vasoconstriction. The care team may use several mitigation strategies to prevent limb ischemia. Arterial and venous complications can be mitigated by careful access site selection, minimizing cannula size, placement of distal perfusion and/or outflow catheter(s), and continuous NIRS monitoring. Rapid intervention, when ischemia or compartment syndrome occurs, can reduce limb loss but may not affect the mortality and morbidity of the ECMO patient in the long term due to their underlying conditions and the etiology of the ECMO need. [ABSTRACT FROM AUTHOR]

Background A widely accepted set of imaging criteria or classification has not yet been adopted to evaluate response to treatment by percutaneous sclerotherapy for aneurysmal bone cyst (ABC). In this article, we described and illustrated the Royal Orthopaedic Hospital (ROH) scoring system which is a new, reproducible, and objective tool to evaluate the radiological response. We also reported our institutional experience in the efficacy of computed tomography (CT)-guided sclerotherapy for treating such lesions. Patients and Methods A retrospective analysis was conducted for 19 patients who underwent CT-guided sclerotherapy with doxycycline and albumin to treat ABC. Follow-up magnetic resonance imaging, at a minimum of 12 months, was assessed according to the four ROH scoring system parameters: cystic component, fluid–fluid level, presence of consolidation, and cortical integrity. The cumulative score was used to grade response as either: excellent, good, equivocal, or poor. Results Out of 19 patients with a mean age of 17.8 years, 11 cases occurred in the long bones, 5 cases in the pelvis, and 1 in each of the C3 vertebral body, scapula, and talus. The mean parameter of response score for cystic component was 2, fluid–fluid level was 1.3, consolidation was 2, and cortical integrity was 2.1. Four cases showed excellent response, 12 cases showed good response, 2 cases showed equivocal response, and 1 case showed poor response. Interrater reliability was excellent (κ = 0.9). Conclusion The ROH scoring system provides the radiologist and surgeon with an objective method to score imaging parameters of response independently and achieve a grade based on the cumulative score. [ABSTRACT FROM AUTHOR]

Introduction: The efficacy of de novo cardiac resynchronisation therapy (CRT) in patients with heart failure (HF), left ventricular systolic dysfunction (LVSD), and a broad QRS morphology is well established. However, the optimal stage for upgrading patients with existing pacemakers (PPMs) or implantable cardioverter-defibrillators (ICDs) and HF with high-burden right ventricular (RV) pacing remains uncertain. Thus, this multicentre retrospective analysis compared patients with pre-existing PPMs or ICDs who underwent CRT upgrades to investigate the appropriate stage for CRT implantation in these patients and to assess the validity of treating both PPM and ICD recipients under the same recommendation level in the current guidelines. Materials and Methods: A total of 151 participants underwent analysis in this study, comprising 93 upgrades to cardiac resynchronisation therapy with pacemaker (CRT-P) and 58 upgrades to cardiac resynchronisation therapy with defibrillator (CRT-D) across three centres in the UK. The aim of the study was to investigate the safety and efficacy of upgrading to CRT from an existing conventional pacemaker or an ICD in the context of high-burden RV pacing. The analysis was conducted separately for each group, assessing changes in echocardiographic parameters, functional New York Heart Association (NYHA) class, and procedure-related complications. Results: The PPM group had a higher percentage RVP burden compared to the ICD group. Post-upgrade, NYHA functional class and EF and LV volumes improved in both groups; however, the response to an upgrade from a pacemaker was greater compared to an upgrade from an ICD. Post-procedural complication risks were similar across the two subgroups but significantly higher compared to de novo implantation. Conclusions: Within the CRT-P subgroup, participants exhibited better responses than their CRT-D counterparts, evident both in echocardiographic improvements and clinical outcomes. Furthermore, patients with non-ischemic cardiomyopathy (NICM) were better responders than those with ischaemic cardiomyopathy. These findings suggest that international guidelines should consider approaching each subgroup separately in the future. [ABSTRACT FROM AUTHOR]

Patients with chronic kidney disease (CKD) are at increased risk of cardiovascular disease. This increased risk cannot be fully explained by traditional risk factors such as hypertension. Endothelial dysfunction and arterial stiffness have been suggested as factors that explain some of the increased risk and are independently associated with important cardiovascular outcomes in patients with CKD. Studies in other disease populations have shown the positive effects of exercise on vascular dysfunction. The aim of this review was to determine whether exercise training interventions improve measures of vascular function and morphology in patients across the spectrum of CKD and which exercise training interventions are most efficacious. A systematic search of Medline, Embase, and the Cochrane Central Register identified 25 randomized controlled trials. Only randomized control trials using an exercise intervention with a nonexercising control group and at least one measure of vascular function or morphology were included. Participants were patients with nondialysis CKD or transplant patients or those requiring dialysis therapy. A systematic review was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A meta-analysis was completed for pulse wave velocity, augmentation index, and measures of endothelium-dependent vasodilation. Data from 25 studies with 872 participants showed that exercise training reduced pulse wave velocity and augmentation index but had no effect on endothelium-dependent vasodilation. Subgroup analyses suggested that exercise interventions of at least moderate intensity were more likely to be effective. Limitations included the absence of observational studies or other interventions aimed at increasing habitual physical activity. Further studies are warranted to investigate which are the most effective exercise interventions. [ABSTRACT FROM AUTHOR]

Objectives: A Rapid Realist Review of social prescribing in Higher Education (HE) was undertaken to determine what works, for whom, how, why, and within what circumstances. The review resulted in the development of a Realist Programme Theory articulating the way in which social prescribing can be implemented within the HE environment. Methods: Searches of 12 electronic databases were supplemented by citation chaining and grey literature surfaced by the Project Advisory Group. The RAMESES Quality Standards for Realist Review were followed, and the retrieved articles were systematically screened and iteratively analysed to develop Context-Mechanism- Outcome Configurations (CMOCs) and an overarching Realist Programme Theory. Results: A total of 57 documents were included. The overarching programme theory was developed from the analysis of these documents and comprised of a social prescribing pathway with the following components: (1) An Accessible Gateway, (2) A Skilled Peer, (3) Trusted-Safe-Credible Resources, and (4) A Healthy Setting. Conclusion: A Realist Programme Theory was developed--this model and associated principles will provide a theoretical basis for the implementation of social prescribing pathways within higher education. Whilst the direct project outputs are of particular significance to the UK HE audience, the underpinning principles can support practice within the global arena. [ABSTRACT FROM AUTHOR]

Aim: The aim of this study was to determine the pre‐discharge carbon dioxide (CO2) levels of preterm neonates with bronchopulmonary dysplasia (BPD) requiring ongoing nasal cannulae oxygen therapy and who were ready for discharge home. Methods: We studied a retrospective cohort of infants born <30 weeks gestational age (GA) at ≥36 weeks corrected GA who had established BPD requiring ongoing nasal cannulae oxygen therapy and were ready for discharge home. Neonates were born and admitted between May 2014 and December 2018. Demographic data at the time of birth and at the time of the last blood gas sampled were collected. Results: One hundred five neonates had median GA of 26.1 weeks and birth weight of 775 g. Median (IQR) CO2 level was 54 (49–58) mmHg. Ninety‐nine (94%) neonates had CO2 levels exceeding the normal range and 91 (87%) neonates had a CO2 between 45 and 65 mmHg. Conclusion: Ninety‐four per cent of neonates <30 weeks GA at ≥36 weeks corrected GA requiring ongoing nasal cannulae oxygen therapy for established BPD, who were ready for discharge home, have CO2 levels outside of normocapnia (35–45 mmHg), with 87% having CO2 levels between 45 and 65 mmHg. [ABSTRACT FROM AUTHOR]

Aim: Noradrenaline (NA) has been used in preterm and term infants for circulatory support due to conditions including sepsis and pulmonary hypertension of the newborn. Treatment in neonates varies widely between institutions and respective neonatologists. The aim of this study is to determine the indications, use and effects of NA in preterm and term infants requiring circulatory support at the Royal Brisbane and Women's Hospital neonatal intensive care unit. We also aim to determine whether there were any differences between neonates who survived versus those who died after NA treatment. Methods: Data were collected from Royal Brisbane and Women's Hospital neonatal unit database including preterm and term infants between 1 January 2016 and 31 May 2021. Analysis included indication for use, blood pressure response, perfusion parameters, haemodynamic indicators and adverse effects. Results: NA treatment was documented in 37 patients requiring treatment of cardiovascular compromise. In 11 (30%) of these infants the indication for use was due to sepsis, 19 (51%) infants had pulmonary hypertension of the newborn, and 7 (19%) infants were diagnosed with hypotension prior to NA administration. Infants who subsequently died (49%) represented a younger gestational age population and exhibited worse cardiac compromise prior to NA administration. Tachycardia occurred in 15 (31%) infants and 1 (2.7%) infant developed transient hypertension. Overall improvement in poor tissue perfusion was seen after NA use. Conclusion: NA use in treating neonates requiring circulatory support appears to be effective. Further prospective trials into NA use as a first‐ or second‐line inotropic agent would be valuable. [ABSTRACT FROM AUTHOR]

Permanent pacing remains a serious complication that can occur in the postoperative period of surgical aortic valve replacement. The reported incidence is variable, and there are many perioperative factors that have been linked with a greater need for permanent pacing. Permanent pacing can also be associated with late lead-related and cardiac complications that can affect late outcome. However, the degree of late dependence on pacemakers is varied, and some studies have shown that a substantial proportion of patients do not need long-term pacing. Some groups have found that permanent pacing was associated with a negative impact on long-term survival in these patients. A common finding among these studies is that the groups of patients with pacemakers had higher preoperative surgical risk and comorbidity status. This makes it difficult to establish whether permanent pacing on its own represents a risk factor for late mortality or whether it is simply a marker that reflects the higher complexity and comorbidities in this group of patients. [ABSTRACT FROM AUTHOR]

This paper discusses the creation and use of the Coronavirus Corpus, which is currently (March 2021) 900 million words in size, and which will probably be about one billion words in size by May–June 2021. The Coronavirus Corpus is a subset of the NOW Corpus (News on the Web), which is currently about 12.1 billion words in size and which grows by about two billion words each year. These two corpora are updated every night, with about 6–10 million words for NOW and 2–3 million words for the Coronavirus Corpus. The Coronavirus Corpus allows users to see the frequency of words and phrases over time (even by individual day), and users can find all words that are more frequent in one time period than another. Users can also see the collocates for words and phrases, and compare the collocates to see what is being said about particular topics over time. [ABSTRACT FROM AUTHOR]

Osteoid osteoma (OO) is a benign bone forming tumor characterized by small size and a disproportionate amount of pain. They are most commonly seen between the ages of 5 and 30 years; however, they can be seen in the older patient albeit infrequently. The hands and feet are the least common site of OO among the extremity bones. We present a case of an OO in the hand of a 77-year-old man who underwent successful treatment with computed tomography–guided percutaneous radiofrequency ablation. We believe this is the oldest recorded patient in the medical literature with a histologically confirmed OO. The condition should therefore be considered in the differential diagnosis of a painful sclerotic bone lesion in this age group to avoid a delay in diagnosis and subsequent treatment. [ABSTRACT FROM AUTHOR]

This paper discusses the creation and use of the TV Corpus (subtitles from 75,000 episodes, 325 million words, 6 English-speaking countries, 1950s-2010s) and the Movies Corpus (subtitles from 25,000 movies, 200 million words, 6 English-speaking countries, 1930s–2010s), which are available at English-Corpora.org. The corpora compare well to the BNC-Conversation data in terms of informality, lexis, phraseology, and syntax. But at 525 million words in total size, they are more than 30 times as large as BNC-Conversation (both BNC1994 and BNC2014 combined), which means that they can be used to look at a wide range of linguistic phenomena. The TV and Movies corpora also allow useful comparisons of very informal language across time (containing texts from the 1930s and later for the movies, and from the 1950s onwards for TV shows) and between dialects of English (such as British and American English). [ABSTRACT FROM AUTHOR]

Bacterial "stand-alone" response regulators (RRs) are pivotal to the control of gene transcription in response to changing cytosolic and extracellular microenvironments during infection. The genome of group A Streptococcus (GAS) encodes more than 30 stand-alone RRs that orchestrate the expression of virulence factors involved in infecting multiple tissues, so causing an array of potentially lethal human diseases. Here, we analysed the molecular epidemiology and biological associations in the coding sequences (CDSs) and upstream intergenic regions (IGRs) of 35 stand-alone RRs from a collection of global GAS genomes. Of the 944 genomes analysed, 97% encoded 32 or more of the 35 tested RRs. The length of RR CDSs ranged from 297 to 1587 nucleotides with an average nucleotide diversity (π) of 0.012, while the IGRs ranged from 51 to 666 nucleotides with average π of 0.017. We present new evidence of recombination in multiple RRs including mga, leading to mga-2 switching, emm-switching and emm-like gene chimerization, and the first instance of an isolate that encodes both mga-1 and mga-2. Recombination was also evident in rofA/nra and msmR loci with 15 emm-types represented in multiple FCT (fibronectin-binding, collagen-binding, T-antigen)-types, including novel emm-type/FCT-type pairings. Strong associations were observed between concatenated RR allele types, and emm-type, MLST-type, core genome phylogroup, and country of sampling. No strong associations were observed between individual loci and disease outcome. We propose that 11 RRs may form part of future refinement of GAS typing systems that reflect core genome evolutionary associations. This subgenomic analysis revealed allelic traits that were informative to the biological function, GAS strain definition, and regional outbreak detection. [ABSTRACT FROM AUTHOR]

Spontaneous intracranial hypotension (SIH) remains a diagnostic and therapeutic challenge. Nonspecific clinical features and a reluctance to treat without confirmatory imaging evidence undermine management. Investigations are often insensitive and expensive, with many patients continuing to an epidural blood patch (EBP) despite negative results. Current diagnostic standards are based on a literature base skewed toward difficult-to-treat cases at specialty centers. This study aims to develop a robust diagnostic and treatment algorithm in real-life clinical practice by 1) investigating the prognostic utility of symptoms of SIH and results of associated investigation from which a scoring system is derived and 2) analyzing the role of EBP as a diagnostic and treatment tool. This is a retrospective study of 86 patients fulfilling clinical criteria for SIH and undergoing EBP, with follow-up ranging from 1 month to 15 years, using patient medical records and an online questionnaire. Although specific and prognostically significant, magnetic resonance imaging of the brain, magnetic resonance imaging of the spine, and symptom-based scoring systems were too insensitive to be of practical use. Most patients with positive and sustained responses to EBP did not meet current criteria for diagnosis. The 72-hour response to the first EBP was found to be highly specific and sensitive in the diagnosis of SIH in our cohort. This study supports the utility of EBP as a safe, accessible, and accurate diagnostic and therapeutic tool. We propose a simple treatment algorithm that facilitates diagnosis, treatment, and prediction of long-term outcomes in this challenging condition. [ABSTRACT FROM AUTHOR]

The diagnosis of tumors and tumorlike lesions of bone is a routine part of both general and specialist radiologic practices. The spectrum of disorders ranges from the small incidental lesion to the potentially life-limiting malignancies whether primary or secondary. In this review, authored by experts from several European orthopaedic oncology centers, we present a collection of pieces of advice in the form of 10 commandments. Adherence in daily practice to this guidance should help minimize adverse patient experiences and outcomes. [ABSTRACT FROM AUTHOR]

Background: One of the most important steps people can take in reducing the spread of bacteria and viruses is washing the hands with soap and water. Frequent washing, required in certain occupations, can lead to skin dryness, chapping, and itching. Materials and methods: In vivo confocal Raman spectroscopy was used to study short‐term effects of hand washing on product deposition, lipid acyl chain structural disordering, and extraction of important skin components such as natural moisturizing factors, cholesterol, ceramides, amino acids, and changes in skin hydration. Effects of use of either soap, synthetic detergent, or triethanolamine (TEA)‐soap/ glycerin were compared at two water temperatures. Results: Soap use resulted in significant deposition at all depths to 20 μm at 25°C and at the surface and 2 μm at 37°C. Significant decreases were observed in relative amounts of all skin components studied. NMF levels were not changed. Skin dehydration was observed for use of soap at 37°C. Conclusions: Short‐term effects of frequent hand washing can be monitored with in vivo confocal Raman spectroscopy. Effects of frequent washing may be reduced with lower wash temperature and products. Skin dehydration is not associated with lipid chain disordering. [ABSTRACT FROM AUTHOR]

Coated nuclear fuel particles, most commonly tri-structural isotropic (TRISO), are intended for use in advanced high temperature reactors. It is vital to understand the mechanical properties of each coating layer to accurately predict the performance of these fuel particles and how these might change at each stage of their lifecycle. This paper reports results of in-situ nanoindentation, with an emphasis on the structural SiC layer, along with microcantilever testing of the critical SiC-IPyC interface. At 1000 °C the hardness of the SiC layer is ∼75% lower than at room temperature implying significantly more plasticity at the reactor operating temperature. The elastic modulus was slightly lower at 1000 °C than at room temperature. Microcantilever fracture at the SiC-IPyC interface shows that failure occurs within the pyrolytic carbon layer rather than an interfacial "debonding" with a strength similar to that of bulk pyrolytic carbon. [ABSTRACT FROM AUTHOR]

Lumbar radicular pain is one of the most commonly encountered clinical syndromes; however, its underlying mechanistic basis, and its relation to the natural history of the disease, are poorly understood. We revieved the available literature to explore the pathophysiology and natural history of lumbar radicular pain. Experimental observations have spawned distinctive, but not mutually exclusive, pathophysiologic descriptions of radicular pain. These mechanisms include mechanical compression and inflammatory processes. In most cases, a complex interplay between these mechanisms is required to sustain the pain. However, when the dorsal root ganglion is mechanically deformed, sustained discharges causing pain can be evoked, leading to pain based on a purely mechanical basis. However, in other instances, previous sensitization of the nerve root by inflammatory processes is required. An understanding of these processes and the natural history of the syndrome is important to developing therapeutic strategies. [ABSTRACT FROM AUTHOR]

The syntactic and semantic properties of the into-causative construction, involving the pattern 'V NP into V-ing', has been studied in some detail, but its historical development has received less attention. This paper looks at the historical shifts in the construction with much more representative and robust corpora than have been used for previous studies. Based on nearly 11,440 tokens from more than 950 million words of text, the paper considers several important changes in the lexical, syntactic, and semantic properties of the construction. The study also establishes the value of large, diverse historical corpora and their role in researching syntactic and semantic change. [ABSTRACT FROM AUTHOR]

Aim: The risk of mortality and morbidity is increased in outborn, extremely premature infants. We aim to determine whether earlier arrival of the retrieval team after the birth of infants less than 29 weeks gestation improves short-term mortality and morbidity.Methods: This is a retrospective analysis of a cohort of infants less than 29 weeks gestation who were retrieved to the Royal Brisbane and Women's Hospital (RBWH) over a 5-year period. Demographic information regarding the infant and mother, retrieval team arrival time and outcome data was collected. Primary outcomes investigated were mortality prior to discharge from hospital or a composite of mortality or severe intraventricular haemorrhage (IVH).Results: Data on 105 infants were analysed; 88 infants (83.8%) survived to discharge home, and 79 (75.2%) survived to discharge without severe IVH. On univariate analysis, there was no significant association between age at arrival of the retrieval team and death prior to discharge (P = 0.94) or death prior to discharge or severe IVH (P = 0.83). On logistic regression analysis, age at arrival of retrieval team remained non-significant for a reduction in death prior to discharge and composite of death or severe IVH (P = 0.70 and P = 0.99, respectively).Conclusion: The earlier arrival of the retrieval team is not associated with improved short-term outcomes in outborn, extremely preterm infants who are retrieved and admitted to a tertiary neonatal intensive care unit - for infants where the retrieval team arrived within about 8 h of birth. [ABSTRACT FROM AUTHOR]

Assessment literacies are finding leverage, but there is little exploration of links between theory, practice and perceived understandings in higher education (HE). This article builds on and consolidates research that has taken place over ten years that evaluates assessment literacies among HE lecturers in education and science, and in staff developers, by presenting a comparative view of the data. The results indicate that there was generally a good understanding of theoretical and practical aspects of summative assessment across all groups. However, understandings of formative assessment showed little concordance between and within the groups, particularly among staff developers, but this group was better at clarifying the necessary link between formative assessment and feedback. Although education lecturers had a firmer grasp of central terminologies, in general there are still deficits in understanding about how these terms interrelate. Staff developers' relative weakness of understanding in some areas is of concern since this group shapes those who teach. These issues are exacerbated by a lack of acknowledgement that they exist, which may seriously hamper the development of both staff and students in clarifying processes they encounter daily. Basic shared understandings are required that can translate into personal, coherent assessment literacies. As a community we need to take on this task, because if we do not, as individuals, or individual groups, we will continue to have fragmented assessment literacies. [ABSTRACT FROM AUTHOR]

This paper presents and tests a method for determining the set of inverse-power coefficients defining the long-range potential tail of a given molecular state by least-squares fitting directly to the energies and inertial rotational constants (Bv ’s) of vibrational levels lying very near dissociation. This approach is superior to the widely used procedure of determining potential points by some inversion procedure and fitting them to the inverse-power form, in that the fit is directly sensitive to the uncertainties in the experimental quantities, and that the parameter uncertainties due to interparameter correlation are greatly reduced. Moreover, the new method gives direct estimates of the number, energies, and other properties of unobserved levels lying above those being fitted. Improved results, including potential parameters up to C10, are presented for the B(3Π+0u) state of I2. [ABSTRACT FROM AUTHOR]

Objective: YouTube® has gained popularity as an unofficial educational resource for surgical trainees, but its content's quality and educational value remain to be evaluated. The aim of this study is to analyze the current content on these techniques for lower extremity DVT (LEDVT) on YouTube®. Methods: A search was performed on YouTube® using 13 search terms in August 2022 on a clear-cached browser. Open-access videos focusing on the surgical techniques of venous thrombolysis or thrombectomy for LEDVT were included. Quality and educational value were assessed and graded based on metrics for accountability (4 items), content (13 items), and production (9 items). Results: Out of 138 videos regarding LEDVT oriented towards medical professionals, only 14 met inclusion criteria. Videos ran for a median of 3.4 min (range 0.37–35.6 min) with a median of 941 views (range 106–54624). Videos scored a median of 5.5 (range 1.0–8.0) out of 11 for content, a median of 2.0 out of 6.0 (range 0.0–2.0) for accountability, and a median of 5.5 out of 9.0 (range 3.0–9.0) for production. Conclusion: Few YouTube® videos focus on the technical aspects of DVT thrombolysis/thrombectomy, and they vary significantly in content with overall poor accountability and production quality. [ABSTRACT FROM AUTHOR]

Several studies in recent years have addressed the impact of phrasal verbs in the English language in an attempt to improve teaching and inform research. While some experts have mentioned the problematic case of separability with these structures, no major attempt to quantify and qualify separable phrasal verbs (SPVs) has been undertaken. Given the prolific nature of these structures, and the documented difficulty they pose for learning and research, we attempt to partially address this issue by finding, counting, and analyzing the SPVs in a mega-corpus of over 1.3 billion words of American and British English. Specifically, we provide and discuss lists of the most frequent SPVs overall, and for those separated by one, two, and three intervening words. We also provide data regarding separability preferences among prolific SPVs, as well as typical grammatical structures of the intervening words between verbs and their allied particles. Implications for instruction and research are discussed throughout the article. [ABSTRACT FROM AUTHOR]

The Adverse Outcome Pathway (AOP) concept is a knowledge assembly and communication tool to facilitate the transparent translation of mechanistic information into outcomes meaningful to the regulatory assessment of chemicals. The AOP framework and associated knowledgebases (KBs) have received significant attention and use in the regulatory toxicology community. However, it is increasingly apparent that the potential stakeholder community for the AOP concept and AOP KBs is broader than scientists and regulators directly involved in chemical safety assessment. In this paper we identify and describe those stakeholders who currently—or in the future—could benefit from the application of the AOP framework and knowledge to specific problems. We also summarize the challenges faced in implementing pathway-based approaches such as the AOP framework in biological sciences, and provide a series of recommendations to meet critical needs to ensure further progression of the framework as a useful, sustainable and dependable tool supporting assessments of both human health and the environment. Although the AOP concept has the potential to significantly impact the organization and interpretation of biological information in a variety of disciplines/applications, this promise can only be fully realized through the active engagement of, and input from multiple stakeholders, requiring multi-pronged substantive long-term planning and strategies. [ABSTRACT FROM AUTHOR]

There is much debate between neonatologists and paediatricians about appropriate oxygen saturation targets for babies with chronic neonatal lung disease (CNLD). Overnight oximetry is used to guide the fraction of inspired oxygen to use. We did this literature review to examine the current literature on the use of overnight oximetry in term infants, preterm infants and babies with CNLD (especially relevant to ex-preterm babies with CNLD going home on oxygen). We reviewed the literature from January 1990 to October 2017 by searching the following databases: Cochrane Central Register of Controlled Trials, The Joanna Briggs Institute, CINAHL, MEDLINE, Scopus, EMBASE, ProQuest and Science Direct. Sixteen articles were included in the review. The literature available on overnight oximetry in neonates is limited, it is not contemporary, and it reports studies that did not use oximeters with modern software for data collection and analysis. It is imperative that reference ranges be defined for overnight oximetry parameters so that babies are not inadvertently administered inappropriate amounts of oxygen. [ABSTRACT FROM AUTHOR]

Aims: Partners and spouses have an important role in supporting healthy self-care in adults with Type 2 diabetes. While evidence has shown that the beliefs held by people with diabetes influence emotional wellbeing, little is known about the long-term impact of partners' illness beliefs on diabetes distress.Methods: Persons with Type 2 diabetes (pwt2d) and their partners completed a questionnaire at baseline (N = 75 couples) and 12 months later (N = 45 couples). Measures included demographic/clinical parameters, the Revised Illness Perception questionnaire, and the Diabetes Distress Scale. A repeated measures ANOVA was used to examine change in measures over time. Multiple regression and moderation analysis were used to explore the indirect influence of partners beliefs on diabetes distress at baseline and follow-up.Results: Illness perceptions and diabetes distress in pwt2d and partners did not change overtime. Partners' beliefs about the controllability, chronicity, and predictability of symptoms of diabetes moderated the relationship between the corresponding pwt2d beliefs and diabetes distress. These indirect effects were observed across both time points.Conclusions: Conflicting illness perceptions about the controllability and chronicity of diabetes, and congruous negative perceptions about diabetes symptoms among couples sustain distress overtime. Targeting the beliefs of couples to improve communication and understanding may reduce diabetes distress. [ABSTRACT FROM AUTHOR]

The focus of this paper is upon the educational background of academic lawyers in England and Wales and the extent to which qualifications from certain institutions may be seen as acting as a proxy for social class. In recent years higher educational background and socio-economic background have been significant topics of research relating to entry to the legal professions and judiciary in England and Wales. There is a relative absence of such research relating to academic lawyers. The research discussed in this paper aims to close that gap. The paper argues that critiques relating to the elite nature of the traditional legal professions in terms of educational background have parallels within the academic legal community, evidenced by a dominance of those educated at Cambridge, Oxford and other Russell Group institutions, with relatively lower proportions of graduates from other sectors, most notably the post-1992 universities. The paper further argues that economic hurdles to entry to an academic legal career are significantly higher than those for other law related careers, potentially exacerbating issues of socio-economic exclusion. The conclusion drawn is that law schools should engage proactively with measures to expand opportunities for entrants into the academic legal community from candidates from a much wider range of educational backgrounds. [ABSTRACT FROM AUTHOR]

Introduction: The COVID-19 pandemic globally impacted healthcare provision. Prescribing changes in common medications can be used as a marker for new diagnoses. We describe how the prescribing of specific psychotropics was impacted by the pandemic. Methods: Primary Care Prescribing data for different classes of drugs from March 2017 to February 2022 were considered. To capture the impact during periods of restricted access to health services for new diagnoses/existing conditions, repeat prescriptions/episodic prescribing were included with account taken of historical trends. The pre-pandemic prescriptions issued each month from March 2018 to February 2020 were linearly extrapolated forward to give an expected annual growth (EAG). The monthly average expected prescriptions for the pandemic period (March 2020–February 2022) were compared. Results: Physical health medications had lower monthly prescriptions during the pandemic, most markedly for antibiotics − 12.5% (EAG − 1.3%). Bronchodilator prescribing showed a marked increase in the early pandemic months from March 2020 of 5% (EAG 0.1%). Mental health medication prescribing increased above trend for hypnotics/anxiolytics by 0.2% (EAG − 2.3%), while antidepressants fell by − 0.2% (EAG 5.0%), with no net change for antipsychotics (EAG 2.8%), but a temporary increase in antipsychotic prescribing in the early pandemic period. For all the main antidepressants prescribed in England (Sertraline, Mirtazapine, Venlafaxine, Fluoxetine and Citalopram), prescribing actually decreased in the main pandemic period vs historical trend. Conclusions: The increase in anxiolytic/hypnotic prescribing above trend links to pandemic effects on anxiety/worry. If anything, there was a slight fall in prescribing of the main antidepressants prescribed, which given prevailing circumstances at the time, suggests that access to services may have restricted access to timely assessment. [ABSTRACT FROM AUTHOR]

This aims to augment what is already known about emotional distress in Type 2 diabetes, by assessing the predictive value of illness perception clusters and relationship quality on four subcategories of Diabetes Distress.162 individuals with Type 2 diabetes responded to a postal questionnaire assessing demographics, depression, diabetes distress, illness perceptions and relationship quality. Long-term blood glucose was retrieved from participants' General Practitioner. Three illness perception clusters emerged from the data, capturing three subgroups of participants sharing similar illness perception schemas. Regression analyses were performed across each diabetes distress subscale, with demographics, illness perception clusters, and relationship variables entered into three blocks. Covariates explained 51.1% of the variance in emotional burden, 41% of the variance in regimen-related distress, 20% of the variance in interpersonal distress, and 8.6% of the variance in physician-related distress. Cluster membership was strongly associated with emotional burden, regimen-related distress, and to a lesser degree interpersonal distress, but was not associated with physician-related distress. Relationship quality most strongly predicted regimen-related distress. Illness perception schemas and interpersonal issues influence emotional adjustment in diabetes. This study provides direction for the content of a novel approach to identifying and reducing diabetes distress in people with Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: Partners have a significant role in a person's ability to adjust to a chronic physical illness, which warrants their inclusion in couples interventions. However to deliver more specific, tailored support it is necessary to explore which types of couples interventions are most effective across certain chronic illness populations and outcomes.Methods: Five databases were searched using selected terms. Thirty-five articles met the eligibility criteria for inclusion.Results: The majority of studies were from the US, and most interventions targeted cancer populations. Couples interventions fell into two categories according to therapeutic approach; Cognitive Behavioural Skills Training (CBST) and Relationship Counselling (RC). When compared with a patient-only intervention or controls, CBST interventions effectively targeted behavioural, physical/somatic and cognitive outcomes, while RC more effectively targeted interpersonal outcomes.Conclusion: Couples interventions can be more effective than patient-only interventions or controls across various patient and partner outcomes. Couples interventions tend to favour a skills-based or a relationship-based approach, which strongly influences the types outcomes effectively targeted.Practice Implications: Our findings suggest it could be therapeutically useful to integrate these two approaches to more holistically support couples living with chronic illness. We also identify the need to target understudied illness groups and ethnicities. [ABSTRACT FROM AUTHOR]

This research focuses on the assessment literacy, that is, the understandings of assessment terminologies and how they relate to each other, in academic staff developers in the UK, collected via questionnaires and semi-structured interviews. Academic staff developers have been trained and certified to support new higher education lecturers in learning, teaching, and assessment practices, and provide continuing professional development for more experienced staff. Results showed inconsistent and differing understandings between and within individuals. These inconsistencies may reflect the lack of consistency of terminology in the literature. This lack of common understanding has far-reaching implications and needs reconciling to enhance personal and collective assessment literacies, particularly since our respondents have responsibility for training the next generation of academics. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is a genetic disorder characterised by highly variable comorbid dysfunction and subsequent morbidity. The mTOR inhibitor everolimus is indicated for the treatment of adult TSC patients with renal angiomyolipomas (AMLs) and for subependymal giant astrocytoma (SEGA) in both adults and children, based on data from the EXIST-1 and EXIST-2 trials. However, due to the historical predominance of everolimus in the oncology setting, some physicians who treat TSC patients may be unfamiliar with everolimus-associated adverse events (AEs) and appropriate management strategies. This article aims to serve as a resource for specialists including nephrologists, paediatricians, neurologists and geneticists who require practical guidance on the management of events such as non-infectious pneumonitis, rash, stomatitis, infections, and renal AEs. Additional consideration is given to drug interactions, hepatic impairment, fertility, and sexual maturation. Since patients with TSC receive clinical benefit from continued therapy, it is important that everolimus-related events are dealt with appropriately through strategies such as dose modification, interruption, the provision of supportive care, regular monitoring, and patient education. [ABSTRACT FROM AUTHOR]

Aim: End-of-life care remains part of the scope of practice in all neonatal units. This study aimed to characterise the end-of-life care provided in an Australian tertiary neonatal centre, where paediatric palliative care was accessible via a consultative service.Methods: This retrospective cohort study examined indicators of quality palliative care provided to 46 infants born within a 30-month period. The cohort included four infants who received palliative care consultations additional to usual neonatal care. The care provided was characterised using descriptive statistics.Results: The most common causes of death were congenital abnormality (37%) and complications of extreme prematurity (22%). Very high proportions of infants and families had family meetings (100%), social worker involvement (100%), memory-making opportunities (100%) and discussion of autopsy (91%). Opiates were prescribed to 76% in the last day of life; most (89%) were administered intravenously. For those prescribed opiates, the median parenteral morphine daily equivalent was 290 mcg/kg/day (interquartile range = 317) in the last 24 h of life. Antenatal resuscitation planning for families of a fetus with a prenatal diagnosis (9%), discussion of preferred location of death (9%), verbal communication with general practitioners (15%) and access to specialised bereavement care (3%) were infrequently provided.Conclusions: At the time of this study, the neonatal unit was not meeting all of the end-of-life care needs of infants and their families. Care was generally more comprehensive when the palliative care service was consulted. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the utility of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions of the pelvis.Materials and Methods: In this retrospective study 33 patients with indeterminate skeletal lesions of the pelvis were evaluated with DWI. Minimum, mean, maximum ADC-values of the skeletal lesions were measured followed by qualitative assessment of DWI. All patients underwent histological confirmation using CT-guided biopsy or surgical resection. The histology of the skeletal lesions was correlated with the findings on DWI.Results: There were 13 malignant lesions and 20 benign lesions. The mean, minimum and maximum ADC values (×10-6mm2/s) for benign skeletal lesions was higher than the mean ADC-values for malignant lesions (1422.2 vs 1263.7; 780.4 vs 771.8; 1969.6 vs 1676.8 respectively). These differences were however not statistically significant (P-values=0.29; 0.94; 0.149 respectively). The sensitivity, specificity, positive predictive value and negative predictive value for qualitative assessment of Diffusion-weighted MRI in the differentiation of benign from malignant skeletal lesions were: 53.9%, 85%, 70%, 73.9% respectively. Qualitative assessment of DWI (restricted diffusion versus non-restricted diffusion) allowed differentiation of benign from malignant skeletal lesions (P-value=0.0259).Conclusions: Qualitative assessment of DWI may aid in the differentiation of benign skeletal lesions from malignant skeletal lesions of the pelvis. Although DWI has a low sensitivity in the distinction of the two disease entities, it may be a useful adjunct due to its relatively high specificity. This is of particular importance in lymphoma where biopsy may only show chronic inflammatory cells and hence may be false negative. [ABSTRACT FROM AUTHOR]

In this paper we offer our comments on “To what extent is the Academic Vocabulary List relevant to university student writing?”. [ABSTRACT FROM AUTHOR]

On the tenth anniversary of two key International Conference on Harmonisation (ICH) guidelines relating to cardiac proarrhythmic safety, an initiative aims to consider the implementation of a new paradigm that combines in vitro and in silico technologies to improve risk assessment. The Comprehensive In Vitro Proarrhythmia Assay (CiPA) initiative (co-sponsored by the Cardiac Safety Research Consortium, Health and Environmental Sciences Institute, Safety Pharmacology Society and FDA) is a bold and welcome step in using computational tools for regulatory decision making. This review compares and contrasts the state-of-the-art tools from empirical to mechanistic models of cardiac electrophysiology, and how they can and should be used in combination with experimental tests for compound decision making. [ABSTRACT FROM AUTHOR]

To determine the extent of group A Streptococcus (GAS) infections in sub-Saharan Africa and the serotypes that cause disease, we analyzed surveillance data for 64,741 hospital admissions in Kilifi, Kenya, during 1998-2011. We evaluated incidence, clinical presentations, and emm types that cause invasive GAS infection. We detected 370 cases; of the 369 for which we had data, most were skin and soft tissue infections (70%), severe pneumonia (23%), and primary bacteremia (14%). Overall case-fatality risk was 12%. Incidence of invasive GAS infection was 0.6 cases/1,000 live births among neonates, 101/100,000 person-years among children <1 year of age, and 35/100,000 among children <5 years of age. Genome sequencing identified 88 emm types. GAS causes serious disease in children in rural Kenya, especially neonates, and the causative organisms have considerable genotypic diversity. Benefit from the most advanced GAS type-specific vaccines may be limited, and efforts must be directed to protect against disease in regions of high incidence. [ABSTRACT FROM AUTHOR]

Academic freedom is central to ideas of higher education, yet in the United Kingdom it is facing challenges from changing managerial approaches within some universities and changing governmental expectations. Universities are increasingly expected to focus upon knowledge which can be shown to have value and to exploit the results of academic enterprise. Resulting constraints on teaching and research by incessant market-driven demands have the potential to compromise academic freedom. This article considers aspects of academic freedom in an increasingly market-driven environment from a lawyer's perspective. The legal protections for academic freedom in the UK are minimal, and consideration of the intellectual property policies of a significant number of UK universities suggests that, in many, academic outputs, especially those relating to teaching, have become subject to more entrepreneurial models of higher education, becoming potentially saleable products to be owned and exploited by universities as they see fit. The position is exacerbated by increasing developments in the use of technology as part of the teaching process. Academics who lose ownership of aspects of their intellectual output risk the undermining of their position and academic freedom with a current employer and limiting their opportunities to change employer. [ABSTRACT FROM AUTHOR]

An editorial is presented on the defining the gap in epicardial pulmonary vein connectivity with high density mapping. Topics include the atrial fibrillation (AF) is the most commonly occurring cardiac arrhythmia in clinical practice and is associated with increasing prevalence and significant morbidity, and the catheter ablation for AF has become an increasingly common therapy after failure with antiarrhythmic drugs to achieve rhythm control.

S almonella Typhimurium isolate D23580 represents a recently identified ST313 lineage of invasive non-typhoidal Salmonellae (i NTS). One of the differences between this lineage and other non-i NTS S. Typhimurium isolates is the presence of prophage BTP1. This prophage encodes a gtr C gene, implicated in O-antigen modification. GtrCBTP1 is essential for maintaining O-antigen length in isolate D23580, since a gtr BTP1 mutant yields a short O-antigen. This phenotype can be complemented by gtrCBTP1 or very closely related gtrC genes. The short O-antigen of the gtrBTP1 mutant was also compensated by deletion of the BTP1 phage tailspike gene in the D23580 chromosome. This tailspike protein has a putative endorhamnosidase domain and thus may mediate O-antigen cleavage. Expression of the gtrCBTP1 gene is, in contrast to expression of many other gtr operons, not subject to phase variation and transcriptional analysis suggests that gtrC is produced under a variety of conditions. Additionally, GtrCBTP1 expression is necessary and sufficient to provide protection against BTP1 phage infection of an otherwise susceptible strain. These data are consistent with a model in which GtrCBTP1 mediates modification of the BTP1 phage O-antigen receptor in lysogenic D23580, and thereby preve nts superinfection by itself and other phage that uses the same O-antigen co-receptor. [ABSTRACT FROM AUTHOR]

Salmonella Typhimurium isolate D23580 represents a recently identified ST313 lineage of invasive nontyphoidal Salmonellae (iNTS). One of the differences between this lineage and other non-iNTS S. Typhimurium isolates is the presence of prophage BTP1. This prophage encodes a gtrC gene, implicated in O-antigen modification. GtrCBTP1 is essential for maintaining O-antigen length in isolate D23580, since a gtrBTP1 mutant yields a short O-antigen. This phenotype can be complemented by gtrCBTP1 or very closely related gtrC genes. The short O-antigen of the gtrBTP1 mutant was also compensated by deletion of the BTP1 phage tailspike gene in the D23580 chromosome. This tailspike protein has a putative endorhamnosidase domain and thus may mediate O-antigen cleavage. Expression of the gtrCBTP1 gene is, in contrast to expression of many other gtr operons, not subject to phase variation and transcriptional analysis suggests that gtrC is produced under a variety of conditions. Additionally, GtrCBTP1 expression is necessary and sufficient to provide protection against BTP1 phage infection of an otherwise susceptible strain. These data are consistent with a model in which GtrCBTP1 mediates modification of the BTP1 phage O-antigen receptor in lysogenic D23580, and thereby prevents superinfection by itself and other phage that uses the same O-antigen co-receptor. [ABSTRACT FROM AUTHOR]

A scarlet fever outbreak began in mainland China and Hong Kong in 2011 (refs. 1-6). Macrolide- and tetracycline-resistant Streptococcus pyogenes emm12 isolates represent the majority of clinical cases. Recently, we identified two mobile genetic elements that were closely associated with emm12 outbreak isolates: the integrative and conjugative element ICE-emm12, encoding genes for tetracycline and macrolide resistance, and prophage ΦHKU.vir, encoding the superantigens SSA and SpeC, as well as the DNase Spd1 (ref. 4). Here we sequenced the genomes of 141 emm12 isolates, including 132 isolated in Hong Kong between 2005 and 2011. We found that the introduction of several ICE-emm12 variants, ΦHKU.vir and a new prophage, ΦHKU.ssa, occurred in three distinct emm12 lineages late in the twentieth century. Acquisition of ssa and transposable elements encoding multidrug resistance genes triggered the expansion of scarlet fever-associated emm12 lineages in Hong Kong. The occurrence of multidrug-resistant ssa-harboring scarlet fever strains should prompt heightened surveillance within China and abroad for the dissemination of these mobile genetic elements. [ABSTRACT FROM AUTHOR]

MyChEMBL is an open virtual platform which provides a free, secure, standardised and easy to use chemoinformatics environment for bioactivity data mining, machine learning, application development, learning and teaching. The main technical features of myChEMBL along with its applications and future plans are discussed here. [ABSTRACT FROM AUTHOR]

ChEMBL Beaker is an open source web framework, exposing a versatile chemistry-focused API (Application Programming Interface) to support the development of new cheminformatics applications. This paper describes the current functionality offered by Beaker and outlines the future technology roadmap. [ABSTRACT FROM AUTHOR]

Introduction Detection of drug-induced pro-arrhythmic risk is a primary concern for pharmaceutical companies and regulators. Increased risk is linked to prolongation of the QT interval on the body surface ECG. Recent studies have shown that multiple ion channel interactions can be required to predict changes in ventricular repolarisation and therefore QT intervals. In this study we attempt to predict the result of the human clinical Thorough QT (TQT) study, using multiple ion channel screening which is available early in drug development. Methods Ion current reduction was measured, in the presence of marketed drugs which have had a TQT study, for channels encoded by hERG, CaV1.2, NaV1.5, KCNQ1/MinK, and Kv4.3/KChIP2.2. The screen was performed on two platforms — IonWorks Quattro (all 5 channels, 34 compounds), and IonWorks Barracuda (hERG & CaV1.2, 26 compounds). Concentration–effect curves were fitted to the resulting data, and used to calculate a percentage reduction in each current at a given concentration. Action potential simulations were then performed using the ten Tusscher and Panfilov (2006), Grandi et al. (2010) and O'Hara et al. (2011) human ventricular action potential models, pacing at 1 Hz and running to steady state, for a range of concentrations. Results We compared simulated action potential duration predictions with the QT prolongation observed in the TQT studies. At the estimated concentrations, simulations tended to underestimate any observed QT prolongation. When considering a wider range of concentrations, and conventional patch clamp rather than screening data for hERG, prolongation of ≥ 5 ms was predicted with up to 79% sensitivity and 100% specificity. Discussion This study provides a proof-of-principle for the prediction of human TQT study results using data available early in drug development. We highlight a number of areas that need refinement to improve the method's predictive power, but the results suggest that such approaches will provide a useful tool in cardiac safety assessment. [ABSTRACT FROM AUTHOR]

UniChem is a low-maintenance, fast and freely available compound identifier mapping service, recently made available on the Internet. Until now, the criterion of molecular equivalence within UniChem has been on the basis of complete identity between Standard InChIs. However, a limitation of this approach is that stereoisomers, isotopes and salts of otherwise identical molecules are not considered as related. Here, we describe how we have exploited the layered structural representation of the Standard InChI to create new functionality within UniChem that integrates these related molecular forms. The service, called `Connectivity Search' allows molecules to be first matched on the basis of complete identity between the connectivity layer of their corresponding Standard InChIs, and the remaining layers then compared to highlight stereochemical and isotopic differences. Parsing of Standard InChI sub-layers permits mixtures and salts to also be included in this integration process. Implementation of these enhancements required simple modifications to the schema, loader and web application, but none of which have changed the original UniChem functionality or services. The scope of queries may be varied using a variety of easily configurable options, and the output is annotated to assist the user to filter, sort and understand the difference between query and retrieved structures. A RESTful web service output may be easily processed programmatically to allow developers to present the data in whatever form they believe their users will require, or to define their own level of molecular equivalence for their resource, albeit within the constraint of identical connectivity. [ABSTRACT FROM AUTHOR]

The "standard" Google Books n-grams were released by Google in 2010, and they include more than 155 billion words of data for the American English data alone. Unfortunately, the standard interface is far too simplistic to allow many types of useful research on this massive dataset. In this paper, I discuss an alternative "advanced" architecture and interface for these datasets, which is freely available at googlebooks.byu.edu. This resource allows for a wide range of research on lexical, phraseological, syntactic, and semantic changes in English, in ways that would not be possible with the standard interface. With this new resource, researchers now have access to hundreds of billions of words of data, and can map out changes in English in ways that were not previously possible. [ABSTRACT FROM AUTHOR]

This article presents our new Academic Vocabulary List (AVL), derived from a 120-million-word academic subcorpus of the 425-million-word Corpus of Contemporary American English (COCA; Davies 2012). We first explore reasons why a new academic core list is warranted, and why such a list is still needed in English language education. We also provide a detailed description of the large academic corpus from which the AVL was derived, as well as the robust frequency and dispersion statistics used to identify the AVL. Our concluding case studies show that the AVL discriminates between academic and other materials, and that it covers ∼14% of academic materials in both COCA (120 million+ words) and the British National Corpus (33 million+ words). The article concludes with a discussion of how the AVL can be used in settings where academic English is the focus of instruction. In this discussion, we introduce a new web-based interface that can be used to learn AVL words, and to identify and interact with AVL words in any text entered in the search window. [ABSTRACT FROM PUBLISHER]

In a letter famous for outlining the genesis of his work The Prince, Machiavelli responded to his friend's description of his day as a courtier in Rome by describing his own daily routine on his farm. The morning he spent bird-catching, taking a book of poetry to pass the time, ‘Dante, Petrarch, or one of the minor poets like Tibullus, Ovid, or some such’. The afternoon was spent at the inn in noisy arguments over games. However, in the evening he goes on:I return home and enter my study; on the threshold I take off my workday clothes, covered with mud and dirt, and put on the garments of court and palace. Fitted out appropriately, I step inside the venerable courts of the ancients, where, solicitously received by them, I nourish myself on that food that alone is mine and for which I was born; where I am unashamed to converse with them and to question them about the motives for their actions, and they, out of their human kindness, answer me. And for four hours at a time I feel no boredom, I forget all my troubles, I do not dread poverty, and I am not terrified by death. I absorb myself into them completely. [ABSTRACT FROM PUBLISHER]