6%) were regarded as novel potentially predictive mutations. Of the nine functionally validated novel mutations, EGFR Y1069C and ERBB2 E936K were transforming in Ba/F3 cells and demonstrated enhanced signaling activity. Mechanistically, the EGFR Y1069C mutation disrupted the binding of the ubiquitin ligase c-CBL to EGFR, whereas the ERBB2 E936K mutation selectively enhanced the activity of ERBB heterodimers. These findings indicate that integrating data from publicly available cell line databases can be used to identify novel, predictive nonhotspot mutations, potentially expanding the patient population benefiting from existing cancer therapies.

Evidence on the association between night work and Parkinson’s disease (PD) is sparse and conflicting, calling for more definitive studies.

We included 20 138 female nurses from the Danish Nurse Cohort without PD who at baseline in 1993 and/or 1999 reported their most common current work schedule (day, evening, night, and rotating (a combination of at least two of these)), including information on lifetime cumulative duration (years) of each shift in a 2009 follow-up survey. We obtained information on PD hospital contacts and PD medication until November 2018 via linkage to the Danish National Patient (inpatient from 1977 and outpatient contacts from 1995 onwards) and Prescription Registers starting in 1995. We defined the incidence of PD as the first-ever hospital contact due to PD, or the first-ever redeemed levodopa prescription, whichever came first. We used Cox regression models to calculate HRs and 95% CIs, adjusting for age, smoking status, coffee consumption and use of hormone replacement therapy.

We found no significant difference in PD risk among nurses who reported working evening (HR=0.86; 95% CI=0.55 to 1.34), night (HR=1.26; 95% CI=0.79 to 2.02) or rotating shifts (HR=0.83; 95% CI=0.56 to 1.21) at cohort baseline in 1993 or 1999, when compared with permanent day workers. Similarly, persistency of shift work (working the same work schedule for 6+ years) or duration of shift work was not associated with PD risk.

Overall, there was little evidence for an association between various shift work schedules including night work and PD in this cohort of middle-aged female nurses.

Overall, there was little evidence for an association between various shift work schedules including night work and PD in this cohort of middle-aged female nurses.

Telomerase gene variants that lead to accelerated telomere shortening are linked to progressive-fibrosing interstitial lung diseases. However, little is known about their relationships with pneumoconiosis. find more This study aimed to identify

variants and leucocyte telomere lengths (LTL) in patients with silicosis or asbestosis.

In the present study, Sanger sequencing of

variants was performed in 193 Chinese Han patients with pneumoconiosis, including 109 with silicosis and 84 with asbestosis. Quantitative PCR was used to measure LTL in peripheral blood of the patients and 200 age and sex-matched healthy controls.

In total, 7.3% patients with pneumoconiosis had 17

variants. Among which 8.3% of patients with silicosis and 3.6% of patients with asbestosis had

variants, respectively. No

variants were detected in silicosis, whereas 3.6% of patients with asbestosis had

variants. Telomeres were significantly shorter in the patients with pneumoconiosis compared with healthy controls (p<0.001). No significant differences in LTL were found between

variant carriers and non-carriers. Exposure to silica dust was associated with the severity of pneumoconiosis after adjusting for covariates (OR 4.92, p=0.002). However,

variants and short telomeres were not associated with the severity of pneumoconiosis.

Telomerase gene variants and short telomeres may be identified in the patients with silicosis and asbestosis in response to the exposure to silica or asbestos dust but are not related to disease severity.

Telomerase gene variants and short telomeres may be identified in the patients with silicosis and asbestosis in response to the exposure to silica or asbestos dust but are not related to disease severity.

Focal therapy has emerged as a promising treatment option for men with localised prostate cancer. However, most of the evaluation of postoperative function has taken place at a relatively high, non-granular level. Most of the data we use to provide informed consent for our patients is obtained from retrospective series, or derived from prospective studies whose primary outcome was oncological. Finally, most studies have focused on erectile function and overlooked other, presumably important, elements of male sexual function. The present study aims at studying in-depth the sexual consequences of focal therapy with various energy sources.

This will be a mixed-methods research study based on a retrospective and prospective cohort, recruited in parallel. The retrospective cohort will consist of patients treated with focal irreversible electroporation, and the prospective cohort of patients treated with three focal therapy energies. Participants will be recruited from two UK urology centres, one National Healtill also be translated into patient information resources (leaflets, online information sheets).

ISRCTN11634296; Pre-results.

ISRCTN11634296; Pre-results.

Introducing primary human papillomavirus (HPV) testing to cervical screening programmes means changes to the results women receive. We explored additional information needs among women undergoing HPV primary screening.

Women were sent a postal questionnaire shortly after receiving their results and 6 and 12 months later. Each questionnaire asked if women had any unanswered questions about cervical screening or HPV testing. Free-text responses constituted the data. Themes were identified using content analysis.

National Health Service (NHS) Cervical Screening Programme, England.

381 women who recorded one or more free-text responses.

The most common theme represented women’s emotional responses and attempts to understand their results. This theme was raised by 45% of women overall, but was as high as 59% in the HPV cleared group. General questions about the cause and epidemiology of HPV were raised by 38% of women and were more common among those testing HPV positive with normal cytology (52%). Questions about the purpose and procedure for HPV testing were most common among HPV-negative women (40%, compared with 16%-24% of the other results groups).