A mouse model of inherited choline kinase ß-deficiency presents with specific cardiac abnormalities and a predisposition to arrhythmia.

The CHKB gene encodes choline kinase ß, which catalyzes the first step in the biosynthetic pathway for the major phospholipid phosphatidylcholine. Homozygous loss-of-function variants in human CHKB are associated with a congenital muscular dystrophy. Dilated cardiomyopathy is present in some CHKB patients and can cause heart failure and death. Mechanisms underlying a cardiac phenotype due to decreased CHKB levels are not well characterized. We determined that there is cardiac hypertrophy in Chkb-/- mice along with a decrease in left ventricle size, internal diameter, and stroke volume compared with wildtype and Chkb+/- mice. Unlike wildtype mice, 60% of the Chkb+/- and all Chkb-/- mice tested displayed arrhythmic events when challenged with isoproterenol. Lipidomic analysis revealed that the major change in lipid level in Chkb+/- and Chkb-/- hearts was an increase in the arrhythmogenic lipid acylcarnitine. An increase in acylcarnitine level is also associated with a defect in the ability of mitochondria to use fatty acids for energy and we observed that mitochondria from Chkb-/- hearts had abnormal cristae and inefficient electron transport chain activity. Atrial natriuretic peptide (ANP) is a hormone produced by the heart that protects against the development of heart failure including ventricular conduction defects. We determined that there was a decrease in expression of ANP, its receptor NPRA, as well as ventricular conduction system markers in Chkb+/- and Chkb-/- mice.

Assessment of association between lower ureteric excision technique and oncological outcomes for upper urinary tract urothelial carcinoma: retrospective analysis from the Scottish Renal Cancer Consortium.

PURPOSE: Nephroureterectomy(NU) remains the gold-standard surgical option for the management of upper urinary tract urothelial carcinoma(UTUC). Controversy exists regarding the optimal excision technique of the lower ureter. We sought to compare post-UTUC bladder tumour recurrence across the Scottish Renal Cancer Consortium(SRCC). METHODS: Patients who underwent NU for UTUC across the SRCC 2012-2019 were identified. The impact of lower-end surgical technique along with T-stage, N-stage, tumour location and focality, positive surgical margin, pre-NU ureteroscopy, upper-end technique and adjuvant mitomycin C administration were assessed by Kaplan-Meier and Cox-regression. The primary outcome was intra-vesical recurrence-free survival (B-RFS). RESULTS: In 402 patients, the median follow-up was 29 months. The lower ureter was managed by open transvesical excision in 90 individuals, transurethral and laparoscopic dissection in 76, laparoscopic or open extra-vesical excision in 31 and 42 respectively, and transurethral dissection and pluck in 163. 114(28.4%) patients had a bladder recurrence during follow-up. There was no difference in B-RFS between lower-end techniques by Kaplan-Meier (p = 0.94). When all factors were taken into account by adjusted Cox-regression, preceding ureteroscopy (HR 2.65, p = 0.001), lower ureteric tumour location (HR 2.16, p = 0.02), previous bladder cancer (HR 1.75, p = 0.01) and male gender (HR 1.61, p = 0.03) were associated with B-RFS. CONCLUSION: These data suggest in appropriately selected patients, lower ureteric management technique does not affect B-RFS. Along with lower ureteric tumour location, male gender and previous bladder cancer, preceding ureteroscopy was associated with a higher recurrence rate following NU, and the indication for this should be carefully considered.

Is early activity resumption after paediatric concussion safe and does it reduce symptom burden at 2 weeks post injury? The Pediatric Concussion Assessment of Rest and Exertion (PedCARE) multicentre randomised clinical trial.

OBJECTIVE: Investigate whether resuming physical activity (PA) at 72 hours post concussion is safe and reduces symptoms at 2 weeks, compared with resting until asymptomatic. METHODS: Real-life conditions, multicentre, single-blinded randomised clinical trial, conducted in three Canadian paediatric emergency departments (ED). Children/youth aged 10-<18 years with acute concussion were recruited between March 2017 and December 2019, and randomly assigned to a 4-week stepwise return-to-PA protocol at 72 hours post concussion even if symptomatic (experimental group (EG)) or to a return-to-PA once asymptomatic protocol (control group (CG)). The primary outcome was self-reported symptoms at 2 weeks using the Health and Behaviour Inventory. Adherence was measured using accelerometers worn 24 hours/day for 14 days post injury. Adverse events (AE) (worsening of symptoms requiring unscheduled ED or primary care visit) were monitored. Multivariable intention-to-treat (ITT) and per-protocol analyses adjusting for prognostically important covariates were examined. Missing data were imputed for the ITT analysis. RESULTS: 456 randomised participants (EG: N=227; mean (SD) age=13.3 (2.1) years; 44.5% women; CG: N=229; mean (SD) age=13.3 (2.2) years; 43.7% women) were analysed. No AE were identified. ITT analysis showed no strong evidence of a group difference at 2 weeks (adjusted mean difference=-1.3 (95% CI:-3.6 to 1.1)). In adherent participants, initiating PA 72 hours post injury significantly reduced symptoms 2 weeks post injury, compared with rest (adjusted mean difference=-4.3 (95% CI:-8.4 to -0.2)). CONCLUSION: Symptoms at 2 weeks did not differ significantly between children/youth randomised to initiate PA 72 hours post injury versus resting until asymptomatic; however, many were non-adherent to the intervention. Among adherent participants, early PA was associated with reduced symptoms at 2 weeks. Resumption of PA is safe and may be associated with milder symptoms at 2 weeks. LEVEL OF EVIDENCE: 1b. TRIAL REGISTRATION NUMBER: NCT02893969. REGISTRY NAME: Pediatric Concussion Assessment of Rest and Exertion (PedCARE).

Building Resilience and Attachment in Vulnerable Adolescents (BRAVA): a brief group intervention for adolescents with mild-to-moderate suicidal ideation and their caregivers.

INTRODUCTION: Suicidal Ideation (SI) is common in adolescents and increases the risk of completed suicide. Few brief interventions have been shown to reduce SI in adolescents. The objective of this study was to evaluate the feasibility of a novel brief group intervention, building resilience and attachment in vulnerable adolescents (BRAVA), designed for adolescents and their caregivers to reduce adolescent SI. METHODS: The study was a pre-post, noncontrolled trial in which 46 adolescents were enrolled in the BRAVA intervention. Adolescents and caregivers completed an intake assessment, six BRAVA group sessions, and an exit assessment 1-week post-BRAVA. RESULTS: Adolescents' SI decreased significantly after completing the BRAVA treatment (pre-post difference = 18.1, 95% CI = 10.01-26.12). Significant improvements in associated symptoms of depression, anxiety, and perceived stress were also observed. Caregivers had reduced perceived stress (pre-post difference = 2.7, 95% CI = 0.30-5.16) and reduction in attachment avoidance (difference = 1.6, 95% CI = 0.29-2.91). Treatment satisfaction was high across the six modules. The rolling entry feature of the intervention allowed participants to begin treatment approximately 2 weeks sooner compared to waiting for the next group cycle. CONCLUSIONS: Study results demonstrate that the BRAVA intervention has the potential to reduce SI among adolescents who present to hospital services in crisis. Further studies are required to establish BRAVA's efficacy in a randomized controlled trial.

Interaction between the STAT4 rs11889341(T) risk allele and smoking confers increased risk of myocardial infarction and nephritis in patients with systemic lupus erythematosus.

OBJECTIVE: To investigate how genetics influence the risk of smoking-related systemic lupus erythematosus (SLE) manifestations. METHODS: Patients with SLE (ndiscovery cohort=776, nreplication cohort=836) were genotyped using the 200K Immunochip single nucleotide polymorphisms (SNP) Array (Illumina) and a custom array. Sixty SNPs with SLE association (p<5.0×10-8) were analysed. Signal transducer and activator of transcription 4 (STAT4) activation was assessed in in vitro stimulated peripheral blood mononuclear cells from healthy controls (n=45). RESULTS: In the discovery cohort, smoking was associated with myocardial infarction (MI) (OR 1.96 (95% CI 1.09 to 3.55)), with a greater effect in patients carrying any rs11889341 STAT4 risk allele (OR 2.72 (95% CI 1.24 to 6.00)) or two risk alleles (OR 8.27 (95% CI 1.48 to 46.27)).Smokers carrying the risk allele also displayed an increased risk of nephritis (OR 1.47 (95% CI 1.06 to 2.03)). In the replication cohort, the high risk of MI in smokers carrying the risk allele and the association between the STAT4 risk allele and nephritis in smokers were confirmed (OR 6.19 (95% CI 1.29 to 29.79) and 1.84 (95% CI 1.05 to 3.29), respectively).The interaction between smoking and the STAT4 risk allele resulted in further increase in the risk of MI (OR 2.14 (95% CI 1.01 to 4.62)) and nephritis (OR 1.53 (95% CI 1.08 to 2.17)), with 54% (MI) and 34% (nephritis) of the risk attributable to the interaction. Levels of interleukin-12-induced phosphorylation of STAT4 in CD8+ T cells were higher in smokers than in non-smokers (mean geometric fluorescence intensity 1063 vs 565, p=0.0063).Lastly, the IL12A rs564799 risk allele displayed association with MI in both cohorts (OR 1.53 (95% CI 1.01 to 2.31) and 2.15 (95% CI 1.08 to 4.26), respectively). CONCLUSIONS: Smoking in the presence of the STAT4 risk gene variant appears to increase the risk of MI and nephritis in SLE. Our results also highlight the role of the IL12-STAT4 pathway in SLE-cardiovascular morbidity.

High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.

OBJECTIVES: To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE). METHODS: Patients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci. RESULTS: SLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9×10-86 and OR 7.48 (6.73 to 8.32), p=2.2×10-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3×10-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0×10-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9×10-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1×10-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0×10-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1×10-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6×10-2), anti-ß2-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8×10-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5×10-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7×10-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6×10-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6×10-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5×10-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3×10-2) in high to low quartile comparison. CONCLUSIONS: A high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.

The HEADS-ED: Evaluating the Clinical Use of a Brief, Action-Oriented, Pediatric Mental Health Screening Tool.

OBJECTIVES: This effectiveness study aimed to evaluate the clinical use of the HEADS-ED tool for patients presenting to a pediatric emergency department (PED) for mental health (MH) care. METHODS: In this pragmatic trial, PED physicians used the HEADS-ED to guide their assessment and identify areas of MH need in 639 patients (mean [SD], 15.16 [1.40] years; female, 72.6%) who presented to the emergency department with MH concerns between May 2013 and March 2014. RESULTS: The HEADS-ED guided consultation to psychiatry/crisis, with 86% receiving a recommended consult. Those with a HEADS-ED score of greater than or equal to 8 and suicidality of 2 (relative risk, 2.64; confidence interval, 2.28-3.06) had a 164% increased risk of physicians requesting a consult compared with those with a score of less than 8 or greater than or equal to 8 with no suicidality of 2. The HEADS-ED mean score was significantly higher for those who received a consult (M = 6.91) than those who did not (M = 4.70; P = 0.000). Similarly, the mean score for those admitted was significantly higher (M = 7.21) than those discharged (M = 5.28; P = 0.000). Agreement on needs requiring action between PED physicians and crisis intervention workers was obtained for a subset of 140 patients and ranged from 62% to 93%. CONCLUSIONS: Results support the HEADS-ED's use by PED physicians to help guide the assessment and referral process and for discussing the clinical needs of patients among health care providers using a common action-oriented language.

Multicentre, randomised clinical trial of paediatric concussion assessment of rest and exertion (PedCARE): a study to determine when to resume physical activities following concussion in children.

INTRODUCTION: Rest until symptom-free, followed by a progressive stepwise return to activities, is often prescribed in the management of paediatric concussions. Recent evidence suggests prolonged rest may hinder recovery, and early resumption of physical activity may be associated with more rapid recovery postconcussion. The primary objective is to determine whether the early reintroduction of non-contact physical activity beginning 72 hours postinjury reduces postconcussive symptoms at 2 weeks in children following an acute concussion as compared with a rest until asymptomatic protocol. METHODS AND ANALYSIS: This study is a randomised clinical trial across three Canadian academic paediatric emergency departments. A total of 350 participants, aged 10-17.99 years, who present within 48 hours of an acute concussion, will be recruited and randomly assigned to either the study intervention protocol (resumption of physical activity 72 hours postconcussion even if experiencing symptoms) or physical rest until fully asymptomatic. Participants will document their daily physical and cognitive activities. Follow-up questionnaires will be completed at 1, 2 and 4 weeks postinjury. Compliance with the intervention will be measured using an accelerometer (24 hours/day for 14 days). Symptoms will be measured using the validated Health and Behaviour Inventory. A linear multivariable model, adjusting for site and prognostically important covariates, will be tested to determine differences between groups. The proposed protocol adheres to the RCT-CONSORT guidelines. DISCUSSION: This trial will determine if early resumption of non-contact physical activity following concussion reduces the burden of concussion and will provide healthcare professionals with the evidence by which to recommend the best timing of reintroducing physical activities. TRIAL REGISTRATION NUMBER: Trial identifier (Clinicaltrials.gov) NCT02893969.

International Consensus Results: Development of Practice Guidelines for Assessment of Peristomal Body and Stoma Profiles, Patient Engagement, and Patient Follow-up.

Evidence indicates that a common problem for the person with an ostomy is pouch leakage and the development of peristomal skin irritation, which can negatively affect quality of life. While it is clear that the pouching system seal leakage can cause profound problems for the person with an ostomy, little information is available on interventions that focus on leakage. To address this gap, an international group of ostomy nurse experts was convened to develop consensus-based practice guidelines to assist ostomy nurses in determining the best pouching system for the patient. The outcomes of these guidelines for the person with a stoma are to decrease leakage and increase security and confidence leading to an increased quality of life. A large-scale Modified Delphi Consensus-Building Process was used to identify key factors in assessing body and stoma profiles to determine the best pouching system. The resulting consensus provides practice guidelines on how to assess body and stoma profiles, engage and educate patients, and when to follow up with patients after hospital discharge or product change.

Creating consensus-based practice guidelines with 2000 nurses.

Medical professionals follow evidence-based practice guidelines to achieve effective patient outcomes. Traditionally, to develop guidelines, a small group of experts examine evidence then agree on a set of statements, which are then published in journals. However, more than 7000 primary care journal articles are published monthly. This study examined a different way of drawing up practice guidelines, which involved large numbers of nurses from different countries directly in developing then disseminating the guidelines to speed up acceptance and the implementation of best practice. The results were consensus-based best practice guidelines for the treatment of patients with ostomies, which have received a high level of acceptance and enthusiasm from practitioners in 27 countries.

The STAT4 SLE risk allele rs7574865[T] is associated with increased IL-12-induced IFN-γ production in T cells from patients with SLE.

OBJECTIVES: Genetic variants in the transcription factor STAT4 are associated with increased susceptibility to systemic lupus erythematosus (SLE) and a more severe disease phenotype. This study aimed to clarify how the SLE-associated intronic STAT4 risk allele rs7574865[T] affects the function of immune cells in SLE. METHODS: Peripheral blood mononuclear cells (PBMCs) were isolated from 52 genotyped patients with SLE. Phosphorylation of STAT4 (pSTAT4) and STAT1 (pSTAT1) in response to interferon (IFN)-α, IFN-γ or interleukin (IL)-12, total levels of STAT4, STAT1 and T-bet, and frequency of IFN-γ+ cells on IL-12 stimulation were determined by flow cytometry in subsets of immune cells before and after preactivation of cells with phytohaemagglutinin (PHA) and IL-2. Cellular responses and phenotypes were correlated to STAT4 risk allele carriership. Janus kinase inhibitors (JAKi) selective for TYK2 (TYK2i) or JAK2 (JAK2i) were evaluated for inhibition of IL-12 or IFN-γ-induced activation of SLE PBMCs. RESULTS: In resting PBMCs, the STAT4 risk allele was neither associated with total levels of STAT4 or STAT1, nor cytokine-induced pSTAT4 or pSTAT1. Following PHA/IL-2 activation, CD8+ T cells from STAT4 risk allele carriers displayed increased levels of STAT4 resulting in increased pSTAT4 in response to IL-12 and IFN-α, and an augmented IL-12-induced IFN-γ production in CD8+ and CD4+ T cells. The TYK2i and the JAK2i efficiently blocked IL-12 and IFN-γ-induced activation of PBMCs from STAT4 risk patients, respectively. CONCLUSIONS: T cells from patients with SLE carrying the STAT4 risk allele rs7574865[T] display an augmented response to IL-12 and IFN-α. This subset of patients may benefit from JAKi treatment.

Value to Whom? The Patient Voice in the Value Discussion.

BACKGROUND: Professional societies and other organizations have recently taken a visible role trying to define treatment value via value frameworks and assessments, providing payer or provider recommendations, and potentially impacting patient access. Patient perspectives routinely differ from those of other stakeholders. Yet, it is not always apparent that patients were engaged in value framework development or assessment. OBJECTIVES: To describe the development and content of the National Health Council's (NHC's) Rubric, a tool that includes criteria for evaluation of value frameworks specifically with regard to patient-centeredness and meaningful patient engagement. METHODS: The NHC held a multistakeholder, invitational roundtable in Washington, DC, in 2016. Participants reviewed existing patient-engagement rubrics, discussed experiences with value frameworks, debated and thematically grouped hallmark patient-centeredness characteristics, and developed illustrative examples of the characteristics. These materials were organized into the rubric, and subsequently vetted via multistakeholder peer review. RESULTS: The resulting rubric describes six domains of patient-centered value frameworks: partnership, transparency, inclusiveness, diversity, outcomes, and data sources. Each domain includes specific examples illustrating how patient engagement and patient-centeredness can be operationalized in value framework processes. CONCLUSIONS: The NHC multistakeholder roundtable's recommendations are captured in the NHC's Rubric to assess value framework and model patient-centeredness and patient engagement. The Rubric is a tool that will be refined over time on the basis of feedback from patient, patient group, framework developer, and other stakeholder-use experiences.

Education in the Waiting Room: Description of a Pediatric Emergency Department Educational Initiative.

OBJECTIVE: The aim of this study was to understand parents' awareness of and reactions to a slide presentation based waiting-room educational initiative. METHODS: This was a prospective observational study at a Canadian tertiary-care pediatric emergency department (ED) with an annual census of 68,000 visits. An anonymous parental survey was developed de novo, and parents were asked to complete the survey during their low-acuity ED visit over a 2-week study period. Descriptive statistics were used to describe responses and themes. RESULTS: Parents completed 520 surveys (733 approached, 70.9% response rate). Eighty-three percent of respondents had previously sought care in the ED. Most parents (68.9%) were aware of the slide presentation, but only 33.7% were able to watch it in its entirety (20 minutes' duration). Of those who watched the whole presentation, 62.9% understood that lower-acuity cases are assessed in the ambulatory zone of the ED, and sicker children are assessed in the acute zone (89.4%), 79.9% felt the presentation helped them to understand how the ambulatory zone functions, and 83.2% appreciated the current wait-time information. General questions about common health concerns were answered correctly in 58.3% (fever), 56.0% (gastroenteritis), 50.5% (abdominal pain/constipation), 35.7% (earache), and 17.0% (head injury). CONCLUSIONS: The majority of parents were aware of this waiting-room educational initiative, but there was variable uptake of information. Parents watching the entire presentation appreciated the information provided, especially wait-time information, and felt it improved their experience. Knowledge of common health conditions was low; novel methods of knowledge transfer must be utilized and evaluated.

A nurse-initiated jaundice management protocol improves quality of care in the paediatric emergency department.

BACKGROUND: Hyperbilirubinemia is a common neonatal condition requiring timely management to prevent acute bilirubin encephalopathy. Management protocols allow nonphysicians to initiate designated actions prior to physician assessment. OBJECTIVE: To assess the effectiveness of a nurse-initiated neonatal jaundice management protocol for serum bilirubin sampling and phototherapy for neonates presenting with hyperbilirubinemia to the Paediatric Emergency Department (PED). METHODS: A health records review was performed for jaundiced neonates 12 months prior to the introduction of the management protocol (control period) and 12 months after (intervention period). Randomly selected charts were evaluated for time to serum bilirubin sampling, phototherapy initiation, ED length of stay, admission rate, completion of direct antiglobulin test and nursing documentation. RESULTS: Two hundred and sixty-six neonates (131 control and 135 intervention) were included. Median time to serum bilirubin sampling was reduced by 22% (36 min versus 28 min; P<0.001) with 34 min difference at the 90th percentile (94 min [95% confidence interval (CI) 63.7 to 116.9] versus 60 min [95% CI 49.0 to 78.2]). Statistically significant improvements were found in time to phototherapy initiation (127 min [95% CI 72.0 to 160.7] versus 65 min [95% CI 50.0 to 72.4] at 90th percentile), ED length of stay (267 min [95% CI 180.9 to 292.9] versus 216 min [95% CI 171.1 to 247.4] at 90th percentile) and hospital admissions (36% versus 17%; P<0.001). Improvements were also observed in direct antiglobulin test measurement (P<0.001) and nursing documentation (P=0.017). CONCLUSIONS: Implementation of a PED neonatal jaundice management protocol was associated with improved timeliness and standardization of care for this common and important condition.

PALB2, which encodes a BRCA2-interacting protein, is a breast cancer susceptibility gene.

PALB2 interacts with BRCA2, and biallelic mutations in PALB2 (also known as FANCN), similar to biallelic BRCA2 mutations, cause Fanconi anemia. We identified monoallelic truncating PALB2 mutations in 10/923 individuals with familial breast cancer compared with 0/1,084 controls (P = 0.0004) and show that such mutations confer a 2.3-fold higher risk of breast cancer (95% confidence interval (c.i.) = 1.4-3.9, P = 0.0025). The results show that PALB2 is a breast cancer susceptibility gene and further demonstrate the close relationship of the Fanconi anemia-DNA repair pathway and breast cancer predisposition.

Biallelic mutations in PALB2 cause Fanconi anemia subtype FA-N and predispose to childhood cancer.

PALB2 was recently identified as a nuclear binding partner of BRCA2. Biallelic BRCA2 mutations cause Fanconi anemia subtype FA-D1 and predispose to childhood malignancies. We identified pathogenic mutations in PALB2 (also known as FANCN) in seven families affected with Fanconi anemia and cancer in early childhood, demonstrating that biallelic PALB2 mutations cause a new subtype of Fanconi anemia, FA-N, and, similar to biallelic BRCA2 mutations, confer a high risk of childhood cancer.

The deSUMOylase SENP7 promotes chromatin relaxation for homologous recombination DNA repair.

SUMO conjugation is known to occur in response to double-stranded DNA breaks in mammalian cells, but whether SUMO deconjugation has a role remains unclear. Here, we show that the SUMO/Sentrin/Smt3-specific peptidase, SENP7, interacts with the chromatin repressive KRAB-associated protein 1 (KAP1) through heterochromatin protein 1 alpha (HP1α). SENP7 promotes the removal of SUMO2/3 from KAP1 and regulates the interaction of the chromatin remodeler CHD3 with chromatin. Consequently, in the presence of CHD3, SENP7 is required for chromatin relaxation in response to DNA damage, for homologous recombination repair and for cellular resistance to DNA-damaging agents. Thus, deSUMOylation by SENP7 is required to promote a permissive chromatin environment for DNA repair.

Examining patient safety attitudes among urology trainees.

OBJECTIVES: To identify current attitudes to patient safety among urology trainees. To examine whether these have changed with the recent increase in emphasis on patient safety and the introduction of new working procedures in operating theatres. SUBJECTS AND METHODS: Subjects included 28 urology trainees, based in the West of Scotland, UK. Trainee attitudes were examined using the Operating Room Management Attitudes Questionnaire, a validated tool for examining attitudes towards patient safety. RESULTS: Attitudes to teamwork were highly positive, with 89-100% of trainees acknowledging the need to share information and conduct pre- and postoperative briefs, and 82-96% being accepting of multidisciplinary feedback on performance. Attitudes to preoperative briefing and multidisciplinary feedback were improved compared with a similar historical cohort. Trainees were reluctant to acknowledge the effect of stress and fatigue on personal performance; 50% felt they worked effectively in critical phases of operations even when tired, only 50% would tell team members their workload was becoming excessive and only 36% of trainees recognized that personal problems could affect their performance. There was no significant change in these attitudes from 2006 data. Regarding leadership and confidence assertion, 68% of trainees felt that leadership in the operating theatre should rest with the medical staff, 18% stated senior decisions or actions should not be questioned unless they threaten safety and 7% that they should not be questioned at all. This was similar to previous data. CONCLUSIONS: Attitudes to briefing and multidisciplinary feedback appear to have improved since the introduction of the World Health Organization surgical checklist and wider use of feedback tools; other safety attitudes remain largely unchanged. Urology trainees may benefit from further training to better understand the mechanisms of error development, to raise awareness of human performance limitation, particularly the effects of stress and fatigue, and to develop techniques to challenge decisions/respond to challenges.

Review of Interventions That Improve Uptake of Lung Cancer Screening: A Cataloging of Strategies That Have Been Shown to Work (or Not).

TOPIC IMPORTANCE: Lung cancer screening (LCS) has the potential to decrease mortality from lung cancer by 20%. Yet, more than a decade since LCS was established as an evidence-based practice, < 20% of the eligible population in the United States has been screened. This review focuses on critically appraising interventions that have been designed to increase the initial uptake of LCS, including how they address known barriers to LCS and their effectiveness in overcoming these barriers. REVIEW FINDINGS: Studies were categorized based on the primary barriers that they addressed: (1) identifying eligible patients (including enhancing awareness through smoking history collection, outreach, and education), (2) shared decision-making-related interventions, and (3) patient navigation interventions. Four of the studies included multicomponent interventions, which often included patient navigation as one of the components. Overall, the effectiveness of the studies reviewed at improving LCS uptake generally was modest and was limited by the multilevel barriers that need to be overcome. Multicomponent interventions generally were more effective at improving LCS uptake, but most studies still had relatively low completion of screening. SUMMARY: Improving uptake of LCS requires learning from prior interventions to design multilevel interventions that address barriers to LCS at key steps and identifying which components of these interventions are effective and generalizable.