"One-size-fits-all"? Observations and Expectations of NLG Systems Across Identity-Related Language Features

Fairness-related assumptions about what constitutes appropriate NLG system behaviors range from invariance, where systems are expected to respond identically to social groups, to adaptation, where responses should instead vary across them. We design and conduct five case studies, in which we perturb different types of identity-related language features (names, roles, locations, dialect, and style) in NLG system inputs to illuminate tensions around invariance and adaptation. We outline people's expectations of system behaviors, and surface potential caveats of these two contrasting yet commonly-held assumptions. We find that motivations for adaptation include social norms, cultural differences, feature-specific information, and accommodation; motivations for invariance include perspectives that favor prescriptivism, view adaptation as unnecessary or too difficult for NLG systems to do appropriately, and are wary of false assumptions. Our findings highlight open challenges around defining what constitutes fair NLG system behavior.Comment: 36 pages, 24 figure

The decisions regarding ADHD management (DRAMa) study: uncertainties and complexities in assessment, diagnosis and treatment, from the clinician's point of view

Clinical decision making is influenced by a range of factors and constitutes an inherently complex task. Here we present results from the decisions regarding ADHD management (DRAMa) study in which we undertook a thematic analysis of clinicians' experiences and attitudes to assessment, diagnosis and treatment of ADHD. Fifty prescribing child psychiatrists and paediatricians from Belgium and the UK took part in semi-structured interviews about their decisions regarding the assessment, diagnosis and treatment of ADHD. Interviews were transcribed and processed using thematic analysis and the principles of grounded theory. Clinicians described the assessment and diagnostic process as inherently complicated and requiring time and experience to piece together the accounts of children made by multiple sources and through the use of varying information gathering techniques. Treatment decisions were viewed as a shared process between families, children, and the clinician. Published guidelines were viewed as vague, and few clinicians spoke about the use of symptom thresholds or specific impairment criteria. Furthermore, systematic or operationalised criteria to assess treatment outcomes were rarely used. Decision making in ADHD is regarded as a complicated, time consuming process which requires extensive use of clinical impression, and involves a partnership with parents. Clinicians want to separate biological from environmental causal factors to understand the level of impairment and the subsequent need for a diagnosis of ADHD. Clinical guidelines would benefit from revisions to take into account the real-world complexities of clinical decision making for ADHD

Obstacles and facilitators to communicating with children about their parents’ mental illness: A qualitative study in a sub-district of Mpumalanga, South Africa

Background Given that common mental disorders are one of the leading causes of disease burden worldwide, it is likely that many children are growing up with a parent or other adult within their family who has anxiety or depression. Parents with a mental illness may not consider it appropriate to discuss their illness with their child, and consequently an absence of communication may lead to stigmatization, shame, misunderstanding their parents’ symptoms, and even blaming themselves. There is a scarcity of research exploring the experiences and perceptions of healthcare professionals about communication with children of parents with mental illness in low-resource and African contexts. Methods A qualitative study using semi-structured interviews with healthcare professionals (n = 15) was conducted within the Bushbuckridge sub-district of Mpumalanga Province, South Africa. Data were analysed using Thematic Analysis. Results Four themes were identified relating to the obstacles around communication with children. These included: (1) finding an appropriate language to describe mental illness, as well as the prevailing cultural explanations of mental illness (2) the stigma associated with mental illness (3) the perceived role of children in society and (4) mental health services and staff skills. Two themes that addressed facilitators of communication about parental mental illness were identified: (1) the potential to increase mental health awareness amongst the broader community through social media, the internet, and general psychoeducation (2) healthcare professionals’ concerns for the wellbeing and future mental health of patients’ children, as well as their hopes for increased mental health awareness amongst future generations. Conclusions This study provides insight into healthcare professionals’ attitudes and perceptions about talking to patients and families within their community about mental illness. The results provide recommendations about possible ways to promote sharing information about a parent’s mental illness with children at an individual and community level. Future research should focus on the collaborative creation of culturally sensitive psychoeducational resources and evidence-based guidelines. This must be supported by systemic and organisational change in order for professionals to successfully facilitate conversations with patients who are parents, and their children

Actin dynamics tune the integrated stress response by regulating eukaryotic initiation factor 2α dephosphorylation.

Four stress-sensing kinases phosphorylate the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α) to activate the integrated stress response (ISR). In animals, the ISR is antagonised by selective eIF2α phosphatases comprising a catalytic protein phosphatase 1 (PP1) subunit in complex with a PPP1R15-type regulatory subunit. An unbiased search for additional conserved components of the PPP1R15-PP1 phosphatase identified monomeric G-actin. Like PP1, G-actin associated with the functional core of PPP1R15 family members and G-actin depletion, by the marine toxin jasplakinolide, destabilised the endogenous PPP1R15A-PP1 complex. The abundance of the ternary PPP1R15-PP1-G-actin complex was responsive to global changes in the polymeric status of actin, as was its eIF2α-directed phosphatase activity, while localised G-actin depletion at sites enriched for PPP1R15 enhanced eIF2α phosphorylation and the downstream ISR. G-actin's role as a stabilizer of the PPP1R15-containing holophosphatase provides a mechanism for integrating signals regulating actin dynamics with stresses that trigger the ISR.This work was funded by the Medical Research Council (UK) (MRC Ref G1002610) and a Wellcome Trust Strategic Award for core facilities to the Cambridge Institute for Medical Research (CIMR, Wellcome 100140). SJM holds a Senior Clinical Research Fellowship from the Medical Research Council (MRC Ref G1002610). DR is a Wellcome Trust Principal Research Fellow (Wellcome 084812/Z/08/Z). The June Hancock Mesothelioma Research Fund funded LED (JH09-2); the British Lung Foundation funded HJC (APHD11-4); CD is a member of the CIMR PhD programme funded by the Wellcome Trust; and VP holds a Diabetes UK Arthur and Sadie Pethybridge PhD Studentship.This is the final published version. It first appeared at http://elifesciences.org/content/4/e04872

Virulence Factors of Pseudomonas aeruginosa Induce Both the Unfolded Protein and Integrated Stress Responses in Airway Epithelial Cells.

Pseudomonas aeruginosa infection can be disastrous in chronic lung diseases such as cystic fibrosis and chronic obstructive pulmonary disease. Its toxic effects are largely mediated by secreted virulence factors including pyocyanin, elastase and alkaline protease (AprA). Efficient functioning of the endoplasmic reticulum (ER) is crucial for cell survival and appropriate immune responses, while an excess of unfolded proteins within the ER leads to "ER stress" and activation of the "unfolded protein response" (UPR). Bacterial infection and Toll-like receptor activation trigger the UPR most likely due to the increased demand for protein folding of inflammatory mediators. In this study, we show that cell-free conditioned medium of the PAO1 strain of P. aeruginosa, containing secreted virulence factors, induces ER stress in primary bronchial epithelial cells as evidenced by splicing of XBP1 mRNA and induction of CHOP, GRP78 and GADD34 expression. Most aspects of the ER stress response were dependent on TAK1 and p38 MAPK, except for the induction of GADD34 mRNA. Using various mutant strains and purified virulence factors, we identified pyocyanin and AprA as inducers of ER stress. However, the induction of GADD34 was mediated by an ER stress-independent integrated stress response (ISR) which was at least partly dependent on the iron-sensing eIF2α kinase HRI. Our data strongly suggest that this increased GADD34 expression served to protect against Pseudomonas-induced, iron-sensitive cell cytotoxicity. In summary, virulence factors from P. aeruginosa induce ER stress in airway epithelial cells and also trigger the ISR to improve cell survival of the host

Изучение байесовского подхода к анализу медико-биологических данных в курсе медицинской и биологической физики

Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III). Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas. Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III

Temporal and external validation of the fullPIERS model for the prediction of adverse maternal outcomes in women with pre-eclampsia

The fullPIERS model is a risk prediction model developed to predict adverse maternal outcomes within 48 h for women admitted with pre-eclampsia. External validation of the model is required before implementation for clinical use. We assessed the temporal and external validity of the fullPIERS model in high income settings using five cohorts collected between 2003 and 2016, from tertiary hospitals in Canada, the United States of America, Finland and the United Kingdom. The cohorts were grouped into three datasets for assessing the primary external, and temporal validity, and broader transportability of the model. The predicted risks of developing an adverse maternal outcome were calculated using the model equation and model performance was evaluated based on discrimination, calibration, and stratification. Our study included a total of 2429 women, with an adverse maternal outcome rate of 6.7%, 6.6%, and 7.0% in the primary external, temporal, and combined (broader) validation cohorts, respectively. The model had good discrimination in all datasets: 0.81 (95%CI 0.75-0.86), 0.82 (95%CI 0.76-0.87), and 0.75 (95%CI 0.71-0.80) for the primary external, temporal, and broader validation datasets, respectively. Calibration was best for the temporal cohort but poor in the broader validation dataset The likelihood ratios estimated to rule in adverse maternal outcomes were high at a cut-off of >= 30% in all datasets. The fullPIERS model is temporally and externally valid and will be useful in the management of women with pre-eclampsia in high income settings although model recalibration is required to improve performance, specifically in the broader healthcare settings.Peer reviewe

Consequences of False-Positive Screening Mammograms

False-positive mammograms, a common occurrence in breast cancer screening programs, represent a potential screening harm that is currently being evaluated by the United States Preventive Services Task Force