MRNIP is a replication fork protection factor

The remodeling of stalled replication forks to form four-way DNA junctions is an important component of the replication stress response. Nascent DNA at the regressed arms of these reversed forks is protected by RAD51 and the tumor suppressors BRCA1/2, and when this function is compromised, stalled forks undergo pathological MRE11-dependent degradation, leading to chromosomal instability. However, the mechanisms regulating MRE11 functions at reversed forks are currently unclear. Here, we identify the MRE11-binding protein MRNIP as a novel fork protection factor that directly binds to MRE11 and specifically represses its exonuclease activity. The loss of MRNIP results in impaired replication fork progression, MRE11 exonuclease–dependent degradation of reversed forks, persistence of underreplicated genomic regions, chemosensitivity, and chromosome instability. Our findings identify MRNIP as a novel regulator of MRE11 at reversed forks and provide evidence that regulation of specific MRE11 nuclease activities ensures protection of nascent DNA and thereby genome integrity

Assessment of offsite, real-time dose measurement systems for emergency situations

An evaluation is made of the effectiveness of fixed, real-time monitoring systems around nuclear power stations in determining the magnitude of unmonitored releases. The effects of meteorological conditions on the accuracy with which the magnitude of unmonitored releases is determined and the uncertainties inherent in defining these meteorological conditions are discussed. The number and placement of fixed field detectors in a system is discussed, and the data processing equipment required to convert field detector output data into release rate information is described. Cost data relative to the purchase and installation of specific systems are given, as well as the characteristics and information return for a system purchased at an arbitrary cost

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided treatment for major depressive disorder and comorbid anxiety disorders: A randomized controlled trial

Disorder-specific cognitive behavior therapy (DS-CBT) is effective at treating major depressive disorder (MDD) while transdiagnostic CBT (TD-CBT) addresses both principal and comorbid disorders by targeting underlying and common symptoms. The relative benefits of these two models of therapy have not been determined. Participants with MDD (n = 290) were randomly allocated to receive an internet delivered TD-CBT or DS-CBT intervention delivered in either clinician-guided (CG-CBT) or self-guided (SG-CBT) formats. Large reductions in symptoms of MDD (Cohen’s d ≥ 1.44; avg. reduction ≥ 45%) and moderate-to-large reductions in symptoms of comorbid generalised anxiety disorder (Cohen’s d ≥ 1.08; avg. reduction ≥ 43%), social anxiety disorder (Cohen’s d ≥ 0.65; avg. reduction ≥ 29%) and panic disorder (Cohen’s d ≥ 0.45; avg. reduction ≥ 31%) were found. No marked or consistent differences were observed across the four conditions, highlighting the efficacy of different forms of CBT at treating MDD and comorbid disorders

Disorder-specific versus transdiagnostic and clinician-guided versus self-guided internet-delivered treatment for panic disorder and comorbid disorders: A randomized controlled trial.

Transdiagnostic cognitive behaviour therapy (TD-CBT) aims to target the symptoms of multiple disorders whereas disorder-specific CBT (DS-CBT) targets the symptoms of principal disorders. This study compared the relative benefits of internet-delivered TD-CBT and DS-CBT when provided in clinician-guided (CG-CBT) and self-guided (SG-CBT) formats for people with a principal diagnosis of Panic Disorder (PD). Participants (n=145) were randomly allocated to receive TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of PD (Cohen's d=0.71; avg. reduction=36%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen's d=0.71; avg. reduction=33%), generalised anxiety disorder (Cohen's d=0.91; avg. reduction=34%) and social anxiety disorder (Cohen's d=0.50; avg. reduction=15%) were found over the 24-month follow-up period. Highlighting their efficacy and acceptability, no marked and consistent differences were observed between TD-CBT and DS-CBT or CG-CBT and DS-CBT

Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for generalized anxiety disorder and comorbid disorders: A randomized controlled trial

© 2015 Z. Generalized anxiety disorder (GAD) can be treated effectively with either disorder-specific cognitive behavior therapy (DS-CBT) or transdiagnostic CBT (TD-CBT). The relative benefits of DS-CBT and TD-CBT for GAD and the relative benefits of delivering treatment in clinician guided (CG-CBT) and self-guided (SG-CBT) formats have not been examined. Participants with GAD (n= 338) were randomly allocated to receive an internet-delivered TD-CBT or DS-CBT intervention delivered in either CG-CBT or SG-CBT formats. Large reductions in symptoms of GAD (Cohen's d= 1.48; avg reduction = 50%) and comorbid major depressive disorder (Cohen's d= 1.64; avg reduction = 45%), social anxiety disorder (Cohen's d= 0.80; avg reduction = 29%) and panic disorder (Cohen's d= 0.55; avg reduction = 33%) were found across the conditions. No substantive differences were observed between DS-CBT and TD-CBT or CG-CBT and SG-CBT, highlighting the public health potential of carefully developed TD-CBT and SG-CBT

Transdiagnostic versus disorder-specific and clinician-guided versus self-guided internet-delivered treatment for Social Anxiety Disorder and comorbid disorders: A randomized controlled trial

Disorder-specific (DS-CBT) and transdiagnostic (TD-CBT) cognitive behaviour therapy have both been used to treat social anxiety disorder (SAD). This study compared internet-delivered DS-CBT and TD-CBT for SAD across clinician-guided (CG-CBT) and self-guided (SG-CBT) formats. Participants with SAD (n = 233) were randomly allocated to receive internet-delivered TD-CBT or DS-CBT and CG-CBT or SG-CBT. Large reductions in symptoms of SAD (Cohen’s d ≥ 1.01; avg. reduction ≥ 30%) and moderate-to-large reductions in symptoms of comorbid depression (Cohen’s d ≥ 1.25; avg. reduction ≥ 39%), generalised anxiety disorder (Cohen’s d ≥ 0.86; avg. reduction ≥ 36%) and panic disorder (Cohen’s d ≥ 0.53; avg. reduction ≥ 25%) were found immediately post-treatment and were maintained or further improved to 24-month follow-up. No marked differences were observed between TD-CBT and DS-CBT or CG-CBT and SG-CBT highlighting the potential of each for the treatment of SAD and comorbid disorders