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Introduction This study implemented MendelScan, a primary care rare disease case-finding tool, into a UK National Health Service population. Rare disease diagnosis is challenging due to disease complexity and low physician awareness. The 2021 UK Rare Diseases Framework highlights as a key priority the need for faster diagnosis to improve clinical outcomes. Methods and results A UK primary care locality with 68,705 patients was examined. MendelScan encodes diagnostic/screening criteria for multiple rare diseases, mapping clinical terms to appropriate SNOMED CT codes (UK primary care standardised clinical terminology) to create digital algorithms. These algorithms were applied to a pseudo-anonymised structured data extract of the electronic health records (EHR) in this locality to \"flag\" at-risk patients who may require further evaluation. All flagged patients then underwent internal clinical review (a doctor reviewing each EHR flagged by the algorithm, removing all cases with a clear diagnosis/diagnoses that explains the clinical features that led to the patient being flagged); for those that passed this review, a report was returned to their GP. 55 of 76 disease criteria flagged at least one patient. 227 (0.33%) of the total 68,705 of EHR were flagged; 18 EHR were already diagnosed with the disease (the highlighted EHR had a diagnostic code for the same RD it was screened for, e.g. Behcet’s disease algorithm identifying an EHR with a SNOMED CT code Behcet's disease). 75/227 (33%) EHR passed our internal review. Thirty-six reports were returned to the GP. Feedback was available for 28/36 of the reports sent. GP categorised nine reports as \"Reasonable possible diagnosis\" (advance for investigation), six reports as \"diagnosis has already been excluded\", ten reports as \"patient has a clear alternative aetiology\", and three reports as \"Other\" (patient left study locality, unable to re-identify accurately). All the 9 cases considered as \"reasonable possible diagnosis\" had further evaluation. Conclusions This pilot demonstrates that implementing such a tool is feasible at a population level. The case-finding tool identified credible cases which were subsequently referred for further investigation. Future work includes performance-based validation studies of diagnostic algorithms and the scalability of the tool.

Goldmark was the first of several composers to write a work based on Heinrich von Kleist's controversial play, Penthesilea. Early critical opinion about the overture was divided. Hanslick found it distasteful, whereas others were thrilled by Goldmark's powerful treatment of the subject. Composed in 1879, during the 1880s Penthesilea became established in orchestral repertoire throughout Europe and America. The overture represents the conflict of violence and sexual attraction between the Queen of the Amazons and Achilles. Exoticism in the play is achieved by contrasting brutal violence, irrational behaviour and extreme sensual passion. This is recreated musically by drawing on topics established in opera. Of particular note is the use of dissonance and unexpected modulations, together with extreme rhythmic and dynamic contrast. A key feature of the music is the interplay between military rhythms representing violence and conflict, and a legato, rocking theme which suggests desire and sensuality.

SINCE the Iowa Writers' Workshop began awarding graduate degrees in poetry and fiction in 1936, the number of MFA programs in creative writing has risen steadily. The focal point of any MFA program is, of course, the writing workshop, in which students read one another's work and offer constructive, respectful criticism.

Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC), yet the mechanisms driving benefit are poorly understood. To identify predictors of clinical benefit to ICB, we performed immunogenomic profiling of tumor samples from patients with relapsed SCLC. Tumors of patients who derive clinical benefit from ICB exhibit cytotoxic T-cell infiltration, high expression of antigen processing and presentation machinery (APM) genes, and low neuroendocrine (NE) differentiation. However, elevated Notch signaling, which positively correlates with low NE differentiation, most significantly predicts clinical benefit to ICB. Activation of Notch signaling in a NE human SCLC cell line induces a low NE phenotype, marked by increased expression of APM genes, demonstrating a mechanistic link between Notch activation, low NE differentiation and increased intrinsic tumor immunity. Our findings suggest Notch signaling as a determinant of response to ICB in SCLC. Immune checkpoint blockade (ICB) benefits only a small subset of patients with small cell lung cancer (SCLC) and the mechanisms driving benefit are poorly understood. Here, the authors show that elevated Notch signaling predicts clinical benefit in ICB in relapsed SCLC.

About a third of strokes cause aphasia, or language loss, with profound consequences for the person's social participation and quality of life. These problems may be mitigated by group social support. But this intervention is not available to all individuals. This study investigated whether it is feasible to deliver group social support to people with aphasia via a multi-user, virtual reality platform. It also explored the indicative effects of intervention and the costs. Intervention aimed to promote wellbeing and communicative success. It enabled participants to form new social connections and share experiences of living with aphasia. It comprised 14 sessions delivered over 6 months and was led by community based co-ordinators and volunteers. Feasibility measures comprised: recruitment and retention rates, compliance with intervention and assessment of treatment fidelity. Effects of intervention were explored using a waitlist randomised controlled design, with outcome measures of wellbeing, communication, social connectedness and quality of life. Two intervention groups were randomised to an immediate condition and two were randomised to a delayed condition. The main analysis explored scores on the measures between two time points, between which those in the immediate condition had received intervention, but those in the delayed group had not (yet). A comprehensive approach to economic data collection ensured that all costs of treatment delivery were recorded. Feasibility findings showed that the recruitment target was met (N = 34) and 85.3% (29/34) of participants completed intervention. All groups ran the 14 sessions as planned, and participants attended a mean of 11.4 sessions (s.d. 2.8), which was 81.6% of the intended dose. Fidelity checking showed minimal drift from the manualised intervention. No significant change was observed on any of the outcome measures, although the study was not powered to detect these. Costs varied across the four groups, from £7,483 - £12,562 British Pounds Sterling ( $10,972 - $ 18,419 US dollars), depending on travel costs, the relative contributions of volunteers and the number of hardware loans that were needed. The results suggest that a larger trial of remote group support, using virtual reality, would be merited. However the treatment content and regime, and the selection of outcome measures should be reviewed before conducting the trial.

I am saddened by Gov. [Sonny Perdue]'s decision not to raise teachers' salaries. Georgia teachers are truly the professional coaches who determine who will play in the game of life and who will wind up as a tackling dummy. Lt. Gov. Mark Taylor is completely off base when he states that \"under Democratic leadership, Georgia has been a fiscally responsible state.\" (\"State should find an alternative to bleeding taxpayers dry,\" @issue, Jan. 16) If that is the case, then I would like Taylor to explain in some terms that all of the people of Georgia can understand just how the state is $620 million in the red, and how it could happen just as our new governor, Sonny Perdue, comes into office. Those who worship [George W. Bush] and wave the flag from their gas hogs, cheering every word the drugstore cowboy stutters, should not oppose the opportunity of matching their hero with the villainous [Bill Clinton]. They constantly wave the latest polls in our faces, declaring that the appointed president is invincible. If they really feel that way, why would they object to matching him with their departed demon?

Aphasia intervention has made increasing use of technology in recent years. The evidence base, which is largely limited to the investigation of spoken language outcomes, indicates positive treatment effects for people with mild to moderate levels of aphasia. Outcomes for those with severe aphasia, however, are less well documented and - where reported - present less consistent gains for measures of spoken output. This study investigates the effects of a purpose-built gesture therapy technology for people with severe aphasia: GeST+. Study outcomes show significant improvement in gesture production abilities for adults with severe aphasia following computer intervention. They indicate no transfer of effects into naming gains or interactive gesture. Outcomes offer encouraging results for computer therapy methods within this hitherto under-researched population but indicate a need for further refinement of interventions in order to maximize persistence of effects and generalization into everyday communication.

Line manager (LM) training in mental health is gaining recognition as an effective method for improving the mental health and wellbeing of workers. However, research predominantly focuses on the impacts of training at the employee-level, often neglecting the broader organisational-level outcomes. Most studies derive insights from LMs using self-reported data, with very few studies examining impacts on organisational-level outcomes. To explore the relationship between LM training in mental health and organisational-level outcomes using company-level data from a diverse range of organisations. This study is a secondary analysis of anonymised panel survey data from firms in England, with data derived from computer-assisted telephone surveys over four waves (2020, 1899 firms; 2021, 1551; 2022, 1904; and 2023, 1902). The analysis merged the four datasets to control for temporal variations. Probit regression was conducted including controls for age of organisation, sector, size, and wave to isolate specific relationships of interest. We found that LM training in mental health is significantly associated with several organisational-level outcomes, including: improved staff recruitment (β = .317, p < .001) and retention (β = .453, p < .001), customer service (β = .453, p < .001), business performance (β = .349, p < .001), and lower long-term sickness absence due to mental ill-health (β = -.132, p < .05). This is the first study to explore the organisational-level outcomes of LM training in mental health in a large sample of organisations of different types, sizes, and sectors. Training LM in mental health is directly related to diverse aspects of an organisations' functioning and, therefore, has strategic business value for organisations. This knowledge has international relevance for policy and practice in workforce health and business performance.