The clinical and cost-effectiveness of a Victim Improvement Package (VIP) for the reduction of chronic symptoms of depression or anxiety in older victims of common crime (the VIP trial): study protocol for a randomised controlled trial.

BACKGROUND: Older people are vulnerable to sustained high levels of psychosocial distress following a crime. A cognitive behavioural therapy (CBT)-informed psychological therapy, the Victim Improvement Package (VIP) may aid recovery. The VIP trial aims to test the clinical and cost-effectiveness of the VIP for alleviating depressive and anxiety symptoms in older victims of crime. METHODS/DESIGN: People aged 65 years or more who report being a victim of crime will be screened by Metropolitan Police Service Safer Neighbourhood Teams within a month of the crime for distress using the Patient Health Questionnaire-2 and the Generalised Anxiety Disorder-2. Those who screen positive will be signposted to their GP for assistance, and re-screened at 3 months. Participants who screen positive for depression and/or anxiety at re-screening are randomised to a CBT informed VIP added to treatment as usual (TAU) compared to TAU alone. The intervention consists of 10 individual 1-h sessions, delivered weekly by therapists from the mental health charity Mind. The primary outcome measure is the Beck Depression Inventory-II (BDI-II) and the Beck Anxiety Inventory (BAI), used as a composite measure, assessed at 6 months after the crime (post therapy) with a 9-month post-crime follow-up. Secondary outcome measures include the EQ-5D, and a modified Client Service Receipt Inventory. A total of 226 participants will be randomised VIP:TAU with a ratio 1:1, in order to detect a standardised difference of at least 0.5 between groups, using a mixed-effects linear-regression model with 90% power and a 5% significance level (adjusting for therapist clustering and potential drop-out). A cost-effectiveness analysis will incorporate intervention costs to compare overall health care costs and quality of life years between treatment arms. An embedded study will examine the impact of past trauma and engagement in safety behaviours and distress on the main outcomes. DISCUSSION: This trial should provide data on the clinical and cost-effectiveness of a CBT-informed psychological therapy for older victims of crime with anxiety and/or depressive symptoms and should demonstrate a model of integrated cross-agency working. Our findings should provide evidence for policy-makers, commissioners and clinicians responding to the needs of older victims of crime. TRIAL REGISTRATION: International Standard Randomised Controlled Trials Number, ID: ISRCTN16929670. Registered on 3 August 2016

Towards designer organelles by subverting the peroxisomal import pathway

The development of ‘designer’ organelles could be a key strategy to enable foreign pathways to be efficiently controlled within eukaryotic biotechnology. A fundamental component of any such system will be the implementation of a bespoke protein import pathway that can selectively deliver constituent proteins to the new compartment in the presence of existing endogenous trafficking systems. Here we show that the protein–protein interactions that control the peroxisomal protein import pathway can be manipulated to create a pair of interacting partners that still support protein import in moss cells, but are orthogonal to the naturally occurring pathways. In addition to providing a valuable experimental tool to give new insights into peroxisomal protein import, the variant receptor-signal sequence pair forms the basis of a system in which normal peroxisomal function is downregulated and replaced with an alternative pathway, an essential first step in the creation of a designer organelle

The Effect of Props on Story Retells in the Classroom

The purpose of this investigation was to determine the effect of props on children’s narrative retells. Forty-two children in two comparable K/1 classrooms heard and practiced the same stories over eight weeks. This study found that the props had a positive effect on the children’s use of descriptive language, but there was no effect on the number of story grammar elements or cohesive devices used, nor for the length and complexity of the stories. Results support a balanced literacy program where children practice retelling stories with and without props

The Transcriptional Response to DNA-Double-Strand Breaks in Physcomitrella patens

The model bryophyte Physcomitrella patens is unique among plants in supporting the generation of mutant alleles by facile homologous recombination-mediated gene targeting (GT). Reasoning that targeted transgene integration occurs through the capture of transforming DNA by the homology-dependent pathway for DNA double-strand break (DNA-DSB) repair, we analysed the genome-wide transcriptomic response to bleomycin-induced DNA damage and generated mutants in candidate DNA repair genes. Massively parallel (Illumina) cDNA sequencing identified potential participants in gene targeting. Transcripts encoding DNA repair proteins active in multiple repair pathways were significantly up-regulated. These included Rad51, CtIP, DNA ligase 1, Replication protein A and ATR in homology-dependent repair, Xrcc4, DNA ligase 4, Ku70 and Ku80 in non-homologous end-joining and Rad1, Tebichi/polymerase theta, PARP in microhomology-mediated end-joining. Differentially regulated cell-cycle components included up-regulated Rad9 and Hus1 DNA-damage-related checkpoint proteins and down-regulated D-type cyclins and B-type CDKs, commensurate with the imposition of a checkpoint at G2 of the cell cycle characteristic of homology-dependent DNA-DSB repair. Candidate genes, including ATP-dependent chromatin remodelling helicases associated with repair and recombination, were knocked out and analysed for growth defects, hypersensitivity to DNA damage and reduced GT efficiency. Targeted knockout of PpCtIP, a cell-cycle activated mediator of homology-dependent DSB resection, resulted in bleomycin-hypersensitivity and greatly reduced GT efficiency

Changes in the Phase of the Annual Cycle of Surface Temperature

The annual cycle in the Earth's surface temperature is extremely large—comparable in magnitude to the glacial–interglacial cycles over most of the planet. Trends in the phase and the amplitude of the annual cycle have been observed, but the causes and significance of these changes remain poorly understood—in part because we lack an understanding of the natural variability. Here we show that the phase of the annual cycle of surface temperature over extratropical land shifted towards earlier seasons by 1.7 days between 1954 and 2007; this change is highly anomalous with respect to earlier variations, which we interpret as being indicative of the natural range. Significant changes in the amplitude of the annual cycle are also observed between 1954 and 2007. These shifts in the annual cycles appear to be related, in part, to changes in the northern annular mode of climate variability, although the land phase shift is significantly larger than that predicted by trends in the northern annular mode alone. Few of the climate models presented by the Intergovernmental Panel on Climate Change reproduce the observed decrease in amplitude and none reproduce the shift towards earlier seasons.Earth and Planetary Science

Performance of Anal Cytology Compared With High-Resolution Anoscopy and Histology in Women With Lower Anogenital Tract Neoplasia

Background: Information on the performance of anal cytology in women who are high-risk for human papillomavirus-related lesions and the factors that might influence it are largely lacking. Aims: Evaluate the performance of anal cytology in women with lower anogenital tract neoplasia. Methods: retrospective study including all new referrals of women with a previous history of anogenital neoplasia, from January 2012 to July 2017, with concomitant anal cytology and high-resolution anoscopy with or without biopsies. Results: 636 anal cytology samples and 323 biopsies were obtained from 278 women. Overall sensitivity and specificity of 'any abnormality' on anal cytology to predict 'any abnormality' in histology was 47% (95% CI 41-54%) and 84% (95% CI 73-91%), respectively. For detecting high-grade squamous intraepithelial lesions (HSIL)/cancer, sensitivity was 71% (95% CI 61-79%) and specificity was 73% (95% CI 66-79%). There was a poor concordance between cytological and histological grades (κ=0.147). Cytology had a higher sensitivity to predict HSIL/cancer in immunosuppressed vs. non-immunosuppressed patients (92% vs. 60%, P=0.002). The sensitivity for HSIL detection was higher when two or more quadrants were affected in comparison with only one (86% vs. 57%, P=0.006). A previous history of vulvar HSIL/cancer (OR 1.71, 1.08-2.73; P=0.023), immunosuppression (OR 1.88, 1.17-3.03; P=0.009) and concomitant genital HSIL/cancer (OR 2.51, 1.47-4.29; P=0.001) were risk factors for abnormal cytology. Conclusions: Patient characteristics can influence the performance of anal cytology in women. The sensitivity for detecting anal HSIL/cancer was higher in those immunosuppressed and with more extensive disease

The mechanism of gene targeting in Physcomitrella patens: homologous recombination, concatenation and multiple integration

The model bryophyte Physcomitrella patens exhibits high frequencies of gene targeting when transformed with DNA constructs containing sequences homologous with genomic loci. ‘Targeted gene replacement’ (TGR) resulting from homologous recombination (HR) between each end of a targeting construct and the targeted locus occurs when either single or multiple targeting vectors are delivered. In the latter instance simultaneous, multiple, independent integration of different transgenes occurs at the targeted loci. In both single gene and ‘batch’ transformations, DNA can also be found to undergo ‘targeted insertion’ (TI), integrating at one end of the targeted locus by HR with one flanking sequence of the vector accompanied by an apparent non-homologous end-joining (NHEJ) event at the other. Untargeted integration at nonhomologous sites also occurs, but at a lower frequency. Molecular analysis of TI at a single locus shows that this occurs as a consequence of concatenation of the transforming DNA, in planta, prior to integration, followed by HR between a single site in the genomic target and two of its repeated homologues in the concatenated vector. This reinforces the view that HR is the major pathway by which transforming DNA is integrated in Physcomitrella

Population‐based cohort study of outcomes following cholecystectomy for benign gallbladder diseases

Background The aim was to describe the management of benign gallbladder disease and identify characteristics associated with all‐cause 30‐day readmissions and complications in a prospective population‐based cohort. Methods Data were collected on consecutive patients undergoing cholecystectomy in acute UK and Irish hospitals between 1 March and 1 May 2014. Potential explanatory variables influencing all‐cause 30‐day readmissions and complications were analysed by means of multilevel, multivariable logistic regression modelling using a two‐level hierarchical structure with patients (level 1) nested within hospitals (level 2). Results Data were collected on 8909 patients undergoing cholecystectomy from 167 hospitals. Some 1451 cholecystectomies (16·3 per cent) were performed as an emergency, 4165 (46·8 per cent) as elective operations, and 3293 patients (37·0 per cent) had had at least one previous emergency admission, but had surgery on a delayed basis. The readmission and complication rates at 30 days were 7·1 per cent (633 of 8909) and 10·8 per cent (962 of 8909) respectively. Both readmissions and complications were independently associated with increasing ASA fitness grade, duration of surgery, and increasing numbers of emergency admissions with gallbladder disease before cholecystectomy. No identifiable hospital characteristics were linked to readmissions and complications. Conclusion Readmissions and complications following cholecystectomy are common and associated with patient and disease characteristics

A ligand-independent origin of abscisic acid perception

Land plants are considered monophyletic, descending from a single successful colonization of land by an aquatic algal ancestor. The ability to survive dehydration to the point of desiccation is a key adaptive trait enabling terrestrialization. In extant land plants, desiccation tolerance depends on the action of the hormone abscisic acid (ABA) that acts through a receptor-signal transduction pathway comprising a PYRABACTIN RESISTANCE 1-like (PYL)–PROTEIN PHOSPHATASE 2C (PP2C)–SNF1-RELATED PROTEIN KINASE 2 (SnRK2) module. Early-diverging aeroterrestrial algae mount a dehydration response that is similar to that of land plants, but that does not depend on ABA: Although ABA synthesis is widespread among algal species, ABA-dependent responses are not detected, and algae lack an ABA-binding PYL homolog. This raises the key question of how ABA signaling arose in the earliest land plants. Here, we systematically characterized ABA receptor-like proteins from major land plant lineages, including a protein found in the algal sister lineage of land plants. We found that the algal PYL-homolog encoded by Zygnema circumcarinatum has basal, ligand-independent activity of PP2C repression, suggesting this to be an ancestral function. Similarly, a liverwort receptor possesses basal activity, but it is further activated by ABA. We propose that co-option of ABA to control a preexisting PP2C-SnRK2-dependent desiccation-tolerance pathway enabled transition from an all-or-nothing survival strategy to a hormone-modulated, competitive strategy by enabling continued growth of anatomically diversifying vascular plants in dehydrative conditions, enabling them to exploit their new environment more efficiently

The acceptability of high resolution anoscopy examination in patients attending a tertiary referral centre

BACKGROUND: High resolution anoscopy (HRA) examination is regarded as the best method for the management of anal high grade squamous intraepithelial lesions to prevent anal squamous carcinoma. However, little is known about the acceptability of this procedure. This analysis looks at patient experience of HRA examination and ablative treatment under local anaesthetic. METHODS: Patients took part in anonymised feedback of their experience immediately after their HRA examinations and/or treatments. A standard questionnaire was used that included assessment of pain and overall satisfaction scores as well as willingness to undergo future HRA examinations. RESULTS: Four hundred four (89.4%) responses were received and all responses were analysed. The group consisted of 119 females (29.4%) and 261 males (64.6%) with median age of 45 years (IQR = 19) and 45 years (IQR = 21) respectively, and included 58 new cases, 53 treatment cases and 202 surveillance cases. 158 patients (39.1%) had at least one biopsy during their visits. The median pain score was 2 [Inter Quartile Range (IQR) 3] on a visual analogue scale of 0 to 10, where 0 indicated no pain / discomfort and 10 indicated severe pain. The median pain score was 2 (IQR 2) in men and 4 (IQR = 3) in women [Dunn's Test = 4.3, p < 0.0001] and 3 (IQR 4.5) in treatment cases. Problematic pain defined as a pain score of ≥7 occurred more frequently in women (14%) than in men (6%), [Chi square test (chi2) = 5.6, p = 0.02]. Patient satisfaction with the care they received, measured on a scale of 0 (not happy) to 10 (very happy) found the median score to be 10 with 76% reporting a score of 10. Out of 360 responses, 98% of women and 99% of men said that they would be willing to have a future HRA examination. CONCLUSIONS: In this cohort, the overall pain scores were low and similar across appointment types. However, women had a higher pain score, including troublesome pain levels. Despite this, both women and men were equally satisfied with their care and were willing to have a future examination. The results of the analysis show that the procedure is acceptable to patient groups. A small number of women may need general anaesthesia for their examinations/treatment