Women Scientists and the Freshwater Biological Association, 1929-1950

In the early to mid-twentieth century, women had limited opportunities to develop and practice as scientists and were subject to being seen as extraordinary women precisely because of their scientific commitment rather than on equal terms as their male counterparts. Opportunities in freshwater science arose in England in a number of interconnected institutions centred on the Freshwater Biological Association (FBA) founded in 1929. Several women scientists pioneering in their fields were nurtured by the FBA, such as early freshwater researchers, Penelope Jenkin, Marie Rosenberg and Winifred Frost, the last two being the first professional women naturalists at the FBA. Other researchers who achieved distinction in their field were also products of the FBA and its imperial and university network: Rosemary Lowe, Winifred Pennington, Kate Ricardo, Carmel Humphries and Maud Godward, for example

Demonstrating the validity of the Video Game Functional Assessment-Revised (VGFA-R)

Problematic video play has been well documented over the course of the last decade. So much so the DSM-5 (APA, 2013) has included problematic video gaming as disorder categorized as Internet Gaming Disorder. The field of applied behavior analysis has been utilizing functional assessments for the last 30 years and has showed evidence of effective results across different populations and environments. Therefore, the purpose of this investigation (comprising three studies) was to validate an indirect functional assessment entitled the Video Game Functional Assessment-Revised (VGFA-R). Using academic experts in the field of video game addiction and applied behavioral analysis (n=6), the first study examined the content validity of the VGFA-R and was able to demonstrate the assessment exceeded the criterion for an established assessment. A second study comprising a survey of 467 gamers examined the factorability by using a confirmatory factor analysis, and found that VGFA-R had an overall variance above .60. Within the third laboratory-based study using gamers (n=11), the VGFA-R was examined for construct validity and found the VGFA-R was able to predict 85% of the appropriate function of behavior. Implications of the study are discussed along with the strengths and limitations of the study and future research directions

Regional differences in prostaglandin E₂ metabolism in human colorectal cancer liver metastases

Background: Prostaglandin (PG) E₂ plays a critical role in colorectal cancer (CRC) progression, including epithelial-mesenchymal transition (EMT). Activity of the rate-limiting enzyme for PGE₂ catabolism (15-hydroxyprostaglandin dehydrogenase [15-PGDH]) is dependent on availability of NAD+. We tested the hypothesis that there is intra-tumoral variability in PGE₂ content, as well as in levels and activity of 15-PGDH, in human CRC liver metastases (CRCLM). To understand possible underlying mechanisms, we investigated the relationship between hypoxia, 15-PGDH and PGE₂ in human CRC cells in vitro. Methods: Tissue from the periphery and centre of 20 human CRCLM was analysed for PGE₂ levels, 15-PGDH and cyclooxygenase (COX)-2 expression, 15-PGDH activity, and NAD+/NADH levels. EMT of LIM1863 human CRC cells was induced by transforming growth factor (TGF) β. Results: PGE₂ levels were significantly higher in the centre of CRCLM compared with peripheral tissue (P = 0.04). There were increased levels of 15-PGDH protein in the centre of CRCLM associated with reduced 15-PGDH activity and low NAD+/NADH levels. There was no significant heterogeneity in COX-2 protein expression. NAD+ availability controlled 15-PGDH activity in human CRC cells in vitro. Hypoxia induced 15-PGDH expression in human CRC cells and promoted EMT, in a similar manner to PGE₂. Combined 15-PGDH expression and loss of membranous E-cadherin (EMT biomarker) were present in the centre of human CRCLM in vivo.Conclusions: There is significant intra-tumoral heterogeneity in PGE₂ content, 15-PGDH activity and NAD+ availability in human CRCLM. Tumour micro-environment (including hypoxia)-driven differences in PGE₂ metabolism should be targeted for novel treatment of advanced CRC

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Modern observations: new ornithology and the science of ourselves, 1920e1940

The emergence and organisation of amateur networks of observation in Britain in the period between 1920 and 1940 are addressed in this paper. It examines the geographical, organisational and epistemological associations between networks of ornithological observation (traced through the British Trust for Ornithology), which emerged from the 1920s, and amateur ethnography (traced through Mass-Observation) which emerged in the late 1930s. I approach these ‘observational cultures’ as spaces which brought together new concepts of the local, of everyday nature and society, as well as the possibilities of changing the everyday. The paper suggests that popular observation during the period partly constituted a reframing of ways of knowing Britain differentiated through the everyday production of natural and social knowledge and the construction of the active citizen and new communities of practice

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure

ContextPatients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy.ObjectiveTo assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition.Design and patientsWe assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE.SettingEndocrine Centres within University Teaching Hospitals in the UK and Ireland.Main outcome measuresUrinary corticosteroid metabolite profile and body composition assessment.ResultsIn study A, when patients were divided into three groups – patients not receiving HC and patients receiving HC≤20 mg/day or HC&gt;20 mg/day – patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls.ConclusionsIn ACTH-deficient patients daily HC doses of &gt;20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype.</jats:sec

Positive Behavioural Support in the UK: A State of the Nation Report

Background: Early Positive Approaches to Support (E-PAtS) is a co-produced and co-facilitated group programme that aims to provide early years support to family caregivers of children with Intellectual and Developmental Disabilities. Method: Thirty-five caregivers who had attended E-PAtS groups took part in individual interviews or focus groups. Caregiver experiences concerning attendance of E-PAtS were explored, in relation to process variables and perceived outcomes. Interviews were thematically analysed. Results: Three major themes were identified: Our Group, Evolving Emotions, and Positive Approaches. Being with and being supported by other families was very important to caregivers. Families reported increased confidence and greater realisation of the need for self-care. Children were reported to show fewer behaviours that challenge and increases in adaptive skills. Findings corresponded to mechanisms and outcomes in the E-PAtS logic model. Conclusion: E-PAtS shows promise as one way families and children with Intellectual and Developmental Disabilities can access early years suppor