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The adsorption capacity of uncalcined and calcined layered double hydroxide (LDH) for fluoride removal was studied in this work. The LDH was synthesized by a co-precipitation method and calcined at various temperatures. The equilibrium data for fluoride adsorption on the LDHs were obtained in a batch adsorber, and the Freundlich isotherm model showed a better fit to the data. The LDH was chemically stable over the pH range of 5-12, but readily dissolved when the pH was below 5. The fluoride adsorption capacity of LDH decreased by raising the pH due to electrostatic interactions, and presented a maximum at 25 °C. The adsorption capacity of LDH was influenced by the calcination temperature and was enhanced by increasing the calcination temperature. The calcination destroyed the crystalline structure of the LDH, which was recovered when the calcined LDH was rehydrated in aqueous solution. The calcined LDH had a very high adsorption capacity towards fluoride. [ABSTRACT FROM AUTHOR]

Purpose To evaluate psychometric characteristics and cross-sectional and longitudinal validity of the 7-item PROMIS® Fatigue Short Form and additional fatigue items among people living with HIV (PLWH) in a nationally distributed network of clinics collecting patient reported data at the time of routine clinical care. Methods: Cross-sectional and longitudinal fatigue data were collected from September 2012 through April 2013 across clinics participating in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS). We analyzed data regarding psychometric characteristics including simulated computerized adaptive testing and differential item functioning, and regarding associations with clinical characteristics. Results: We analyzed data from 1597 PLWH. Fatigue was common in this cohort. Scores from the PROMIS® Fatigue Short Form and from the item bank had acceptable psychometric characteristics and strong evidence for validity, but neither performed better than shorter instruments already integrated in CNICS. Conclusions: The PROMIS® Fatigue Item Bank is a valid approach to measuring fatigue in clinical care settings among PLWH, but in our analyses did not perform better than instruments associated with less respondent burden. Electronic supplementary material The online version of this article (doi:10.1186/s12981-017-0146-y) contains supplementary material, which is available to authorized users.

We studied the response of Brachionus patulus to different concentrations of the heavy metal Pb in the presence and absence of sediments. We conducted acute (LC50) and chronic (life table demography and population growth) toxicity tests using sediment levels of 0, 30 and 280 mg l−1 (=0, 17 and 170 NTU) and Pb at 0, 0.06 and 0.6 mg l−1. Experiments were conducted at 20 ± 1°C on a horizontal shaker and algal food ( Chlorella vulgaris) was added at a density of 1.0 × 106 cells ml−1. The median lethal concentration (LC50 ± 95% Confidence intervals) of PbCl2 for B. patulus was 6.15 ± 1.08 mg l−1. Age-specific survivorship and fecundity curves showed increase in turbidity level resulted in decreased survival and offspring production of the rotifers. Increase in Pb concentration too had a negative effect on the survival and reproductive output of B. patulus. Statistically, average lifespan, life expectancy at birth, gross and net reproductive rates and the rate of population increase were all significantly influenced by the concentration of Pb, turbidity level as well as the interaction of Pb concentration × turbidity level. Rotifers exposed to 170 NTU did not grow regardless of the heavy metal concentration in the medium. Similarly, B. patulus exposed to 0.6 mg l−1 Pb did not survive beyond 10 days regardless of the turbidity level in the medium. The rate of population increase of B. patulus derived from the growth experiments was negative in all treatments containing Pb as low as 0.06 mg l−1 or turbidity level as low as 17 NTU. In treatments containing Pb or sediments, there existed no relation between the egg ratio and the population density. [ABSTRACT FROM AUTHOR]

We observed the effects of sodium bicarbonate supplement on bone mass in rats on strenuous treadmill training. Sixty female Wistar rats (93-days-old; mean initial weight 261 +/- 16 g) were studied. One group of 15 rats was killed at the beginning of the experiments (basal control group), while another group of 15 rats was not manipulated (Exer-NaB-). Another group of 15 rats was exercised but did not receive sodium bicarbonate (Exer+NaB-), while the final group of 15 rats exercised and received sodium bicarbonate (Exer+NaB+) at a dose of 0.05 mg/kg/day, administered by esophageal catheter on exercise days. These rats were killed at the end of 11 weeks. Femoral and vertebral length, weight, and bone mineral content (BMC) and density (BMD) were measured. According to ANOVA with the Tukey-Kramer test, femur length and weight, vertebral weight, femur BMC and BMD, vertebral BMC and BMD and the ratio between femur and vertebral BMC and final body weight, and plasma bicarbonate were lower in the basal control and Exer+NaB- groups than in the two other groups (P < 0.005-0.0001). Overall, there was a positive correlation between femur and vertebral BMC and femur BMC and length (P < 0.0001 for all). Only in the Exer+NaB- group was there a positive association between plasma bicarbonate levels and femur length (r = 0.78; P < 0.0005). Our study demonstrates the adverse effects of strenuous exercise on bone, and the usefulness of sodium bicarbonate supplements in preventing and minimized these effects. [ABSTRACT FROM AUTHOR]

BACKGROUND: Long-term patient-reported outcomes are needed to inform treatment decisions for localized prostate cancer. METHODS: Patient-reported outcomes of 1643 randomly assigned participants in the ProtecT (Prostate Testing for Cancer and Treatment) trial were evaluated to assess the functional and quality-of-life impacts of prostatectomy, radiotherapy with neoadjuvant androgen deprivation, and active monitoring. This article focuses on the outcomes of the randomly assigned participants from 7 to 12 years using mixed effects linear and logistic models. RESULTS: Response rates exceeded 80% for most measures. Among the randomized groups over 7 to 12 years, generic quality-of-life scores were similar. Among those in the prostatectomy group, urinary leakage requiring pads occurred in 18 to 24% of patients over 7 to 12 years, compared with 9 to 11% in the active monitoring group and 3 to 8% in the radiotherapy group. In the prostatectomy group, 18% reported erections sufficient for intercourse at 7 years, compared with 30% in the active monitoring and 27% in the radiotherapy groups; all converged to low levels of potency by year 12. Nocturia (voiding at least twice per night) occurred in 34% in the prostatectomy group compared with 48% in the radiotherapy group and 47% in the active monitoring group at 12 years. Fecal leakage affected 12% in the radiotherapy group compared with 6% in the other groups by year 12. The active monitoring group experienced gradual age-related declines in sexual and urinary function, avoiding radical treatment effects unless they changed management. CONCLUSIONS: ProtecT provides robust evidence about continued impacts of treatments in the long term. These data allow patients newly diagnosed with localized prostate cancer and their clinicians to assess the trade-offs between treatment harms and benefits and enable better informed and prudent treatment decisions. (Funded by the UK National Institute for Health and Care Research Health Technology Assessment Programme projects 96/20/06 and 96/20/99; ISRCTN number, ISRCTN20141297; ClinicalTrials.gov number, NCT02044172.)

Objective: To investigate the functional and quality of life (QoL) outcomes of treatments for localised prostate cancer and inform treatment decision-making., Patients and Methods: Men aged 50-69 years diagnosed with localised prostate cancer by prostate-specific antigen testing and biopsies at nine UK centres in the Prostate Testing for Cancer and Treatment (ProtecT) trial were randomised to, or chose one of, three treatments. Of 2565 participants, 1135 men received active monitoring (AM), 750 a radical prostatectomy (RP), 603 external-beam radiotherapy (EBRT) with concurrent androgen-deprivation therapy (ADT) and 77 low-dose-rate brachytherapy (BT, not a randomised treatment). Patient-reported outcome measures (PROMs) completed annually for 6 years were analysed by initial treatment and censored for subsequent treatments. Mixed effects models were adjusted for baseline characteristics using propensity scores., Results: Treatment-received analyses revealed different impacts of treatments over 6 years. Men remaining on AM experienced gradual declines in sexual and urinary function with age (e.g., increases in erectile dysfunction from 35% of men at baseline to 53% at 6 years and nocturia similarly from 20% to 38%). Radical treatment impacts were immediate and continued over 6 years. After RP, 95% of men reported erectile dysfunction persisting for 85% at 6 years, and after EBRT this was reported by 69% and 74%, respectively (P < 0.001 compared with AM). After RP, 36% of men reported urinary leakage requiring at least 1 pad/day, persisting for 20% at 6 years, compared with no change in men receiving EBRT or AM (P < 0.001). Worse bowel function and bother (e.g., bloody stools 6% at 6 years and faecal incontinence 10%) was experienced by men after EBRT than after RP or AM (P < 0.001) with lesser effects after BT. No treatment affected mental or physical QoL., Conclusion: Treatment decision-making for localised prostate cancer can be informed by these 6-year functional and QoL outcomes., (© 2022 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objectives: To evaluate the long-term oncological outcomes of patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU) and the impact of diagnostic ureteroscopy (URS) on survival outcomes., Materials and Methods: A retrospective analysis of all consecutive patients undergoing RNU for suspected UTUC at a UK tertiary referral centre from a prospectively maintained database was conducted. The primary outcome measures were 5- and 10-year cancer-specific survival (CSS). The secondary outcomes were: overall survival (OS), recurrence-free survival (RFS), impact of prior diagnostic URS on OS, CSS and intravesical RFS (intravesical-RFS), and predictors of intravesical recurrence. Statistical analysis was performed in R using the 'survminer' and 'survival' packages. The Kaplan-Meier method was used to calculate survival functions and these were expressed in graphical form. Uni-/multivariate survival analyses were performed using the Cox proportional hazard regression model. Statistical significance in this study was set at P < 0.05., Results: A total of 422 patients underwent RNU with confirmed UTUC. The median (interquartile range) follow-up of patients with confirmed UTUC was 9.2 (5.6-12.7) years. The 5- and 10-year CSS rates were 70.5% (95% confidence interval [CI] 65.9-74.9) and 67.1% (95% CI 62.4-71.6), respectively. OS (HR 1.04 [95% CI 0.78-1.38]; P = 0.46) and CSS (HR 0.96 [95% CI 0.68-1.34]; P = 0.81) were similar in the diagnostic URS and the direct RNU cohorts. intravesical RFS was superior for the direct RNU cohort (HR 1.94 [95% CI 1.19-3.17]; P = 0.008). In multivariate analysis, prior URS, T2 stage, proximal ureter tumour and bladder cancer history were predictors of metachronous bladder recurrence., Conclusion: This single-centre retrospective cohort study reports the long-term oncological outcomes of RNU with a median follow-up of 9.2 years, serving as a reference standard in counselling patients undergoing RNU. Stage and grade of the RNU specimen were the only two studied factors that appeared to adversely impact long-term CSS and OS. Our results suggest that the risk of intravesical recurrence is increased nearly twofold in patients who have undergone diagnostic URS prior to RNU. Prior URS, however, does not appear to adversely impact long-term CSS and OS. The authors suggest that a risk-stratified approach be adopted, wherein diagnostic URS is offered only in equivocal cases., (© 2021 The Authors BJU International © 2021 BJU International.)

Background: Androgen suppression is a central component of prostate cancer management but causes substantial long-term toxicity. Transdermal administration of oestradiol (tE2) circumvents first-pass hepatic metabolism and, therefore, should avoid the cardiovascular toxicity seen with oral oestrogen and the oestrogen-depletion effects seen with luteinising hormone releasing hormone agonists (LHRHa). We present long-term cardiovascular follow-up data from the Prostate Adenocarcinoma Transcutaneous Hormone (PATCH) trial programme., Methods: PATCH is a seamless phase 2/3, randomised, multicentre trial programme at 52 study sites in the UK. Men with locally advanced or metastatic prostate cancer were randomly allocated (1:2 from August, 2007 then 1:1 from February, 2011) to either LHRHa according to local practice or tE2 patches (four 100 μg patches per 24 h, changed twice weekly, reducing to three patches twice weekly if castrate at 4 weeks [defined as testosterone ≤1·7 nmol/L]). Randomisation was done using a computer-based minimisation algorithm and was stratified by several factors, including disease stage, age, smoking status, and family history of cardiac disease. The primary outcome of this analysis was cardiovascular morbidity and mortality. Cardiovascular events, including heart failure, acute coronary syndrome, thromboembolic stroke, and other thromboembolic events, were confirmed using predefined criteria and source data. Sudden or unexpected deaths were attributed to a cardiovascular category if a confirmatory post-mortem report was available and as other relevant events if no post-mortem report was available. PATCH is registered with the ISRCTN registry, ISRCTN70406718; the study is ongoing and adaptive., Findings: Between Aug 14, 2007, and July 30, 2019, 1694 men were randomly allocated either LHRHa (n=790) or tE2 patches (n=904). Overall, median follow-up was 3·9 (IQR 2·4-7·0) years. Respective castration rates at 1 month and 3 months were 65% and 93% among patients assigned LHRHa and 83% and 93% among those allocated tE2. 157 events from 145 men met predefined cardiovascular criteria, with a further ten sudden deaths with no post-mortem report (total 167 events in 153 men). 26 (2%) of 1694 patients had fatal cardiovascular events, 15 (2%) of 790 assigned LHRHa and 11 (1%) of 904 allocated tE2. The time to first cardiovascular event did not differ between treatments (hazard ratio 1·11, 95% CI 0·80-1·53; p=0·54 [including sudden deaths without post-mortem report]; 1·20, 0·86-1·68; p=0·29 [confirmed group only]). 30 (34%) of 89 cardiovascular events in patients assigned tE2 occurred more than 3 months after tE2 was stopped or changed to LHRHa. The most frequent adverse events were gynaecomastia (all grades), with 279 (38%) events in 730 patients who received LHRHa versus 690 (86%) in 807 patients who received tE2 (p<0·0001) and hot flushes (all grades) in 628 (86%) of those who received LHRHa versus 280 (35%) who received tE2 (p<0·0001)., Interpretation: Long-term data comparing tE2 patches with LHRHa show no evidence of a difference between treatments in cardiovascular mortality or morbidity. Oestrogens administered transdermally should be reconsidered for androgen suppression in the management of prostate cancer., Funding: Cancer Research UK, and Medical Research Council Clinical Trials Unit at University College London., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Trichomes are a common morphological defense against pests, in particular, type IV glandular trichomes have been associated with resistance against different invertebrates. Cultivated tomatoes usually lack or have a very low density of type IV trichomes. Therefore, for sustainable management of this crop, breeding programs could incorporate some natural defense mechanisms, such as those afforded by trichomes, present in certain Solanum species. We have identified a S. pimpinellifolium accession with very high density of this type of trichomes. This accession was crossed with a S. lycopersicum var. cerasiforme and a S. lycopersicum var. lycopersicum accessions, and the two resulting F2 populations have been characterized and genotyped using a new genotyping methodology, K-seq. We have been able to build an ultra-dense genetic map with 147,326 SNP markers with an average distance between markers of 0.2 cm that has allowed us to perform a detailed mapping. We have used two different families and two different approaches, QTL mapping and QTL-seq, to identify several QTLs implicated in the control of trichome type IV developed in this accession on the chromosomes 5, 6, 9 and 11. The QTL located on chromosome 9 is a major QTL that has not been previously reported in S. pimpinellifolium . This QTL could be easily introgressed in cultivated tomato due to the close genetic relationship between both species.

Objectives: Active surveillance (AS) enables men with low risk, localised prostate cancer (PCa) to avoid radical treatment unless progression occurs; lack of reliable AS protocols to determine progression leaves uncertainties for men and clinicians. This study investigated men's strategies for coping with the uncertainties of active monitoring (AM, a surveillance strategy within the Prostate testing for cancer and Treatment, ProtecT trial) over the longer term and implications for optimising supportive care., Design: Longitudinal serial in-depth qualitative interviews every 2-3 years for a median 7 (range 6-14) years following diagnosis., Setting: Four centres within the UK Protect trial., Participants: Purposive sample of 20 men with localised PCa: median age at diagnosis 64 years (range 52-68); 15 (75%) had low-risk PCa; 12 randomly allocated to, 8 choosing AM. Eleven men continued with AM throughout the study period (median 7 years). Nine received radical treatment after a median 4 years (range 0.8-13.8 years)., Intervention: AM: 3-monthly serum prostate-specific antigen (PSA)-level assessment (year 1), 6-12 monthly thereafter; increase in PSA ≥50% during previous 12 months or patient/clinician concern triggered review., Main Outcomes: Thematic analysis of 73 interviews identified strategies to accommodate uncertainty and anxiety of living with untreated cancer; implications for patient care., Results: Men sought clarity, control or reassurance, with contextual factors mediating individual responses. Trust in the clinical team was critical for men in balancing anxiety and facilitating successful management change/continued monitoring. Only men from ProtecT were included; men outside ProtecT may have different experiences., Conclusion: Men looked to clinicians for clarity, control and reassurance. Where provided, men felt comfortable continuing AM or having radical treatments when indicated. Clinicians build patient trust by clearly describing uncertainties, allowing patients control wherever possible and being aware of how context influences individual responses. Insights indicate need for supportive services to build trust and patient engagement over the long term., Trial Registration Number: ISRCTN20141297; Pre-results., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Background: There is limited evidence relating to the cost-effectiveness of treatments for localised prostate cancer., Methods: The cost-effectiveness of active monitoring, surgery, and radiotherapy was evaluated within the Prostate Testing for Cancer and Treatment (ProtecT) randomised controlled trial from a UK NHS perspective at 10 years' median follow-up. Prostate cancer resource-use collected from hospital records and trial participants was valued using UK reference-costs. QALYs (quality-adjusted-life-years) were calculated from patient-reported EQ-5D-3L measurements. Adjusted mean costs, QALYs, and incremental cost-effectiveness ratios were calculated; cost-effectiveness acceptability curves and sensitivity analyses addressed uncertainty; subgroup analyses considered age and disease-risk., Results: Adjusted mean QALYs were similar between groups: 6.89 (active monitoring), 7.09 (radiotherapy), and 6.91 (surgery). Active monitoring had lower adjusted mean costs (£5913) than radiotherapy (£7361) and surgery (£7519). Radiotherapy was the most likely (58% probability) cost-effective option at the UK NICE willingness-to-pay threshold (£20,000 per QALY). Subgroup analyses confirmed radiotherapy was cost-effective for older men and intermediate/high-risk disease groups; active monitoring was more likely to be the cost-effective option for younger men and low-risk groups., Conclusions: Longer follow-up and modelling are required to determine the most cost-effective treatment for localised prostate cancer over a man's lifetime., Trial Registration: Current Controlled Trials number, ISRCTN20141297: http://isrctn.org (14/10/2002); ClinicalTrials.gov number, NCT02044172: http://www.clinicaltrials.gov (23/01/2014).

Background: Prostate cancer is the most common cancer among men in the UK. Prostate-specific antigen testing followed by biopsy leads to overdetection, overtreatment as well as undertreatment of the disease. Evidence of treatment effectiveness has lacked because of the paucity of randomised controlled trials comparing conventional treatments., Objectives: To evaluate the effectiveness of conventional treatments for localised prostate cancer (active monitoring, radical prostatectomy and radical radiotherapy) in men aged 50-69 years., Design: A prospective, multicentre prostate-specific antigen testing programme followed by a randomised trial of treatment, with a comprehensive cohort follow-up., Setting: Prostate-specific antigen testing in primary care and treatment in nine urology departments in the UK., Participants: Between 2001 and 2009, 228,966 men aged 50-69 years received an invitation to attend an appointment for information about the Prostate testing for cancer and Treatment (ProtecT) study and a prostate-specific antigen test; 82,429 men were tested, 2664 were diagnosed with localised prostate cancer, 1643 agreed to randomisation to active monitoring ( n  = 545), radical prostatectomy ( n  = 553) or radical radiotherapy ( n  = 545) and 997 chose a treatment., Interventions: The interventions were active monitoring, radical prostatectomy and radical radiotherapy., Trial Primary Outcome Measure: Definite or probable disease-specific mortality at the 10-year median follow-up in randomised participants., Secondary Outcome Measures: Overall mortality, metastases, disease progression, treatment complications, resource utilisation and patient-reported outcomes., Results: There were no statistically significant differences between the groups for 17 prostate cancer-specific ( p  = 0.48) and 169 all-cause ( p  = 0.87) deaths. Eight men died of prostate cancer in the active monitoring group (1.5 per 1000 person-years, 95% confidence interval 0.7 to 3.0); five died of prostate cancer in the radical prostatectomy group (0.9 per 1000 person-years, 95% confidence interval 0.4 to 2.2 per 1000 person years) and four died of prostate cancer in the radical radiotherapy group (0.7 per 1000 person-years, 95% confidence interval 0.3 to 2.0 per 1000 person years). More men developed metastases in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring, n  = 33 (6.3 per 1000 person-years, 95% confidence interval 4.5 to 8.8); radical prostatectomy, n  = 13 (2.4 per 1000 person-years, 95% confidence interval 1.4 to 4.2 per 1000 person years); and radical radiotherapy, n  = 16 (3.0 per 1000 person-years, 95% confidence interval 1.9 to 4.9 per 1000 person-years; p  = 0.004). There were higher rates of disease progression in the active monitoring group than in the radical prostatectomy and radical radiotherapy groups: active monitoring ( n  = 112; 22.9 per 1000 person-years, 95% confidence interval 19.0 to 27.5 per 1000 person years); radical prostatectomy ( n  = 46; 8.9 per 1000 person-years, 95% confidence interval 6.7 to 11.9 per 1000 person-years); and radical radiotherapy ( n  = 46; 9.0 per 1000 person-years, 95% confidence interval 6.7 to 12.0 per 1000 person years; p  < 0.001). Radical prostatectomy had the greatest impact on sexual function/urinary continence and remained worse than radical radiotherapy and active monitoring. Radical radiotherapy's impact on sexual function was greatest at 6 months, but recovered somewhat in the majority of participants. Sexual and urinary function gradually declined in the active monitoring group. Bowel function was worse with radical radiotherapy at 6 months, but it recovered with the exception of bloody stools. Urinary voiding and nocturia worsened in the radical radiotherapy group at 6 months but recovered. Condition-specific quality-of-life effects mirrored functional changes. No differences in anxiety/depression or generic or cancer-related quality of life were found. At the National Institute for Health and Care Excellence threshold of £20,000 per quality-adjusted life-year, the probabilities that each arm was the most cost-effective option were 58% (radical radiotherapy), 32% (active monitoring) and 10% (radical prostatectomy)., Limitations: A single prostate-specific antigen test and transrectal ultrasound biopsies were used. There were very few non-white men in the trial. The majority of men had low- and intermediate-risk disease. Longer follow-up is needed., Conclusions: At a median follow-up point of 10 years, prostate cancer-specific mortality was low, irrespective of the assigned treatment. Radical prostatectomy and radical radiotherapy reduced disease progression and metastases, but with side effects. Further work is needed to follow up participants at a median of 15 years., Trial Registration: Current Controlled Trials ISRCTN20141297., Funding: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 24, No. 37. See the National Institute for Health Research Journals Library website for further project information., Competing Interests: Malcolm Mason reports personal fees from Sanofi (Paris, France), Bayer (Leverkusen, Germany) and Janssen Pharmaceutica (Beerse, Belgium) outside the submitted work. Derek Rosario reports grants from Bayer and personal fees from Ferring Pharmaceuticals (Saint-Prex, Switzerland) outside the submitted work. Jane Blazeby was a member of the following during the project: National Institute for Health Research (NIHR) Health Technology Assessment (HTA) Clinical Trials and Evaluation Committee (2009–2013), HTA NIHR Obesity (2010–2012), Commissioning Board for HTA Surgery Themed Call Board and the NIHR Clinical Trials Unit (CTU) Standing Advisory Committee (2015–2019). Jenny Donovan was a member of the following during the project: HTA Commissioning Board (2006–12), Rapid Trials and Add-on Studies Board (2012), NIHR Senior Investigator panel (2009–12) and NIHR Health Services and Delivery Research board (Deputy Chairperson) (2010–11). Freddie C Hamdy was a member of the following during the project: HTA Commissioning Board (2007–12) and HTA Surgery Themed Call Board (2012–13). J Athene Lane was a member of the following during the project: CTUs funded by NIHR (2017 to present). Chris Metcalfe was a member of the following during the project: CTUs funded by NIHR (2010 to present). Tim Peters was a member of the following during the project: HTA Medicines for Children Themed Call (2005–6) and NIHR CTU Standing Advisory Committee (2008–14). John Staffurth reports support for travel to conferences and attendance on an advisory board from Bayer. Emma L Turner reports grants from Cancer Research UK (London, UK) during the conduct of the study.

We report the case of a 14-year-old girl that was referred to the maxillo facial surgery unit at age 11 years because she exhibited swelling in the right side of her maxilla and right mandible. After a conservative surgery, she started with interferon alpha-2a to avoid recurrence. She has remained in treatment with successful results during her follow up. Considerable reduction of both maxilla and mandible lesions and bone fill have been documented. In addition, her clinical history and phenotype were suggestive of Noonan syndrome. She has short stature, broad and short neck; hypertelorism (increased distance between the eyes); downslanting palpebral fissures; sparse eyebrows and eyelashes; posteriorly rotated ears with fleshy lobes; follicular keratosis over the face, and developmental delay. Her karyotype was 46, XX. Molecular analysis of RAS/MAPK pathway genes showed a SOS1 amino acid substitution of arginine to lysine at position 552 (p.R552K). This case presents the infrequent condition of Noonan syndrome with multiple giant cell lesions (NS/MGCL) that would be the first patient as far as we know treated with surgery and interferon alpha-2a for her giant cell lesions., (© 2020 Wiley Periodicals, Inc.)

A collection of 163 accessions, including Solanum pimpinellifolium , Solanum lycopersicum var. cerasiforme and Solanum lycopersicum var. lycopersicum , was selected to represent the genetic and morphological variability of tomato at its centers of origin and domestication: Andean regions of Peru and Ecuador and Mesoamerica. The collection is enriched with S. lycopersicum var. cerasiforme from the Amazonian region that has not been analyzed previously nor used extensively. The collection has been morphologically characterized showing diversity for fruit, flower and vegetative traits. Their genomes were sequenced in the Varitome project and are publicly available (solgenomics.net/projects/varitome). The identified SNPs have been annotated with respect to their impact and a total number of 37,974 out of 19,364,146 SNPs have been described as high impact by the SnpEeff analysis. GWAS has shown associations for different traits, demonstrating the potential of this collection for this kind of analysis. We have not only identified known QTLs and genes, but also new regions associated with traits such as fruit color, number of flowers per inflorescence or inflorescence architecture. To speed up and facilitate the use of this information, F2 populations were constructed by crossing the whole collection with three different parents. This F2 collection is useful for testing SNPs identified by GWAs, selection sweeps or any other candidate gene. All data is available on Solanaceae Genomics Network and the accession and F2 seeds are freely available at COMAV and at TGRC genebanks. All these resources together make this collection a good candidate for genetic studies., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s) 2020.)

Background: The ProtecT trial reported intention-to-treat analysis of men with localised prostate cancer (PCa) randomly allocated to active monitoring (AM), radical prostatectomy, and external beam radiotherapy., Objective: To determine report outcomes according to treatment received in men in randomised and treatment choice cohorts., Design, Setting, and Participants: This study focuses on secondary care. Men with clinically localised prostate cancer at one of nine UK centres were invited to participate in the treatment trial comparing AM, radical prostatectomy, and radiotherapy., Intervention: Two cohorts included 1643 men who agreed to be randomised; 997 declined randomisation and chose treatment., Outcome Measurements and Statistical Analysis: Health-related quality of life impacts on urinary, bowel, and sexual function were assessed using patient-reported outcome measures. Analysis was carried out based on treatment received for each cohort and on pooled estimates using meta-analysis. Differences were estimated with adjustment for known prognostic factors using propensity scores., Results and Limitations: According to treatment received, more men receiving AM died of PCa (AM 1.85%, surgery 0.67%, radiotherapy 0.73%), whilst this difference remained consistent with chance in the randomised cohort (p=0.08); stronger evidence was found in the exploratory analyses (randomised plus choice cohort) when AM was compared with the combined radical treatment group (p=0.003). There was also strong evidence that metastasis (AM 5.6%, surgery 2.4%, radiotherapy 2.7%) and disease progression (AM 20.35%, surgery 5.87%, radiotherapy 6.62%) were more common in the AM group. Compared with AM, there were higher risks of sexual dysfunction (95% at 6mo) and urinary incontinence (55% at 6mo) after surgery, and of sexual dysfunction (88% at 6mo) and bowel dysfunction (5% at 6mo) after radiotherapy. The key limitations are the potential for bias when comparing groups defined by treatment received and outdating of the interventions being evaluated during the lengthy follow-up required in trials of screen-detected PCa., Conclusions: Analyses according to treatment received showed increased rates of disease-related events and lower rates of patient-reported harms in men managed by AM compared with men managed by radical treatment, and stronger evidence of greater PCa mortality in the AM group., Patient Summary: More than 90 out of every 100 men with localised prostate cancer do not die of prostate cancer within 10yr, irrespective of whether treatment is by means of monitoring, surgery, or radiotherapy. Side effects on sexual and bladder function are much better after active monitoring, but the risks of spreading of prostate cancer are more common., (Copyright © 2019 The Author(s). Published by Elsevier B.V. All rights reserved.)