Clinical effectiveness of online computerised cognitive-behavioural therapy without support for depression in primary care: randomised trial

BACKGROUND: Computerised cognitive-behavioural therapy (CCBT) might offer a solution to the current undertreatment of depression. AIMS: To determine the clinical effectiveness of online, unsupported CCBT for depression in primary care. METHOD: Three hundred and three people with depression were randomly allocated to one of three groups: Colour Your Life; treatment as usual (TAU) by a general practitioner; or Colour Your Life and TAU combined. Colour Your Life is an online, multimedia, interactive CCBT programme. No assistance was offered. We had a 6-month follow-up period. RESULTS: No significant differences in outcome between the three interventions were found in the intention-to-treat and per protocol analyses. CONCLUSIONS: Online, unsupported CCBT did not outperform usual care, and the combination of both did not have additional effects. Decrease in depressive symptoms in people with moderate to severe depression was moderate in all three interventions. Online CCBT without support is not beneficial for all individuals with depressio

The BEST study - a prospective study to compare business class versus economy class air travel as a cause of thrombosis

Background. As many as 10% of airline passengers travelling without prophylaxis for long distances may develop a venous thrombosis. There is, however, no evidence that economy class travellers are at increased risk of thrombosis.Objectives. A suitably powered prospective study, based on the incidence of deep-vein thrombosis (DVT) reported in previous studies on long-haul flights, was designed to determine the incidence of positive venous duplex scans and D-dimer elevations in low and intermediate-risk passengers, comparing passengers travelling in business and economy class.Patients/methods. Eight hundred and ninety-nine passengers were recruited (180 travelling business class and 719 travelling economy). D-dimers were measured before and after the flight. A value greater than 500 ng/ml was accepted as abnormal. A thrombophilia screen was conducted which included the factor V Leiden mutation, the prothombin 20210A mutation, protein C and S levels, antithrombin levels, and anticardiolipin antibodies immunoglobulin G (IgG) and immunoglobulin M (IgM). On arrival, lower limb compression ultrasonography of the deep veins was performed. Logistical regression analysis was used to determine the risk factors related to abnormally high D-dimer levels.Results. Only 434 subjects had a full venous duplex scan performed. None had ultrasonic evidence of venous thrombosis. Nine passengers tested at departure had elevated D-dimer levels and these volunteers were excluded from further study. Seventy-four of the 899 passengers had raised D-dimers on arrival. Twenty-two of 180 business class passengers (12%) developed elevated D-dimers compared with 52 of 719 economy class passengers (7%). There was no significant association between elevation of D-dimers and the class flown (odds ratio (OR) 0.61, p = 0.109). The factor V Leiden mutation, factor VIII levels and the use of aspirin were, however, associated with raised D-dimers (OR 3.36, p = 0.024; OR 1.01, p = 0.014; and OR 2.04, p = 0.038, respectively). Five hundred and five passengers were contacted within 6 months and none reported any symptoms of a clinical thrombosis or pulmonary embolus.Conclusion. The incidence of ultrasonically proven DVT is much lower than previously reported. However, more than 10% of all passengers developed raised D-dimers, which were unrelated to the class flown. A rise in D-dimers is associated with an inherent risk of thrombosis and/ or thrombophilia, demonstrates activation of both the coagulation and fibrinolytic systems during long-haul flights, and may indicate the development of small thrombi

Water Management Solution of Reservoir Storage Function Under Condition of Measurement Uncertainties in Hydrological Input Data

AbstractThe paper describes a possible procedure of the rate uncertainty implementation to the continuous water stage measurement and uncertainties of state - discharge rating curve point positions, which the stage -discharge rating curves were fitted into the uncertainties of the real discharge series members. Then the members of discharge series under uncertainty impact were tested on the calculated values of the reservoir storage volume. The next step was the implementation of the uncertainties of the real discharge series members on the generation of the artificial discharge series of mean monthly discharge using the AR and ARMA generators and the determination of their impact on the calculated values of the reservoir storage volume

An exploratory study on the potential of social enterprise to act as the institutional glue of network governance

This study combines two topics of contemporary salience for public administration: social enterprise and governance networks. While operating at different levels, both are institutions which attempt to draw together the three pillars of state, market, and civil society. Nevertheless, the respective literatures focus on particular aspects of the three pillars. We connect the two concepts and suggest that some social enterprises can act as the institutional glue of networks due to their ability to benefit organizations in each of the three sectors. This requires social enterprises to have the managerial capacity to diffuse social know-how, and is facilitated by the trust of other organizations and a supportive policy framework. The links are explicated at the conceptual level before providing evidence from South Korea and the UK. Finally, research propositions are offered, which suggest new avenues for future research

High prevalence of non-accidental trauma among deceased children presenting at Level I trauma centers in the Netherlands

PURPOSE: Between 0.1—3% of injured children who present at a hospital emergency department ultimately die as a result of their injuries. These events are typically reported as unnatural causes of death and may result from either accidental or non-accidental trauma (NAT). Examples of the latter include trauma that is inflicted directly or resulting from neglect. Although consultation with a forensic physician is mandatory for all deceased children, the prevalence of fatal inflicted trauma or neglect among children is currently unclear. METHODS: This is a retrospective study that included children (0–18 years) who presented and died at one of the 11 Level I trauma centers in the Netherlands between January 1, 2014, and January 1, 2019. Outcomes were classified based on the conclusions of the Child Abuse and Neglect team or those of forensic pathologists and/or the court in cases referred for legally mandated autopsies. Cases in which conclusions were unavailable and there was no clear accidental cause of death were reviewed by an expert panel. RESULTS: The study included 175 cases of childhood death. Seventeen (9.7%) of these children died due to inflicted trauma (9.7%), 18 (10.3%) due to neglect, and 140 (80%) due to accidents. Preschool children (< 5 years old) were significantly more likely to present with injuries due to inflicted trauma and neglect compared to older children (44% versus 6%, p < 0.001, odds ratio [OR] 5.80, 95% confidence interval [CI] 2.66–12.65). Drowning accounted for 14 of the 18 (78%) pediatric deaths due to neglect, representing 8% of the total cases. Postmortem radiological studies and autopsies were performed on 37 (21%) of all cases of childhood death. CONCLUSION: One of every five pediatric deaths in our nationwide Level I trauma center study was attributed to NAT; 44% of these deaths were the result of trauma experienced by preschool-aged children. A remarkable number of fatal drownings were due to neglect. Postmortem radiological studies and autopsies were performed in only one-fifth of all deceased children. The limited use of postmortem investigations may have resulted in missed cases of NAT, which will result in an overall underestimation of fatal NAT experienced by children. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12024-021-00416-7

The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells

Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration of BRCA1-independent homologous recombination through loss of factors such as 53BP1, RIF1, and REV7/MAD2L2, which inhibit end resection of DNA double-strand breaks (DSBs). To identify additional factors involved in this process, we performed CRISPR/SpCas9-based loss-of-function screens and selected for factors that confer PARP inhibitor (PARPi) resistance in BRCA1-deficient cells. Loss of members of the CTC1-STN1-TEN1 (CST) complex were found to cause PARPi resistance in BRCA1-deficient cells in vitro and in vivo. We show that CTC1 depletion results in the restoration of end resection and that the CST complex may act downstream of 53BP1/RIF1. These data suggest that, in addition to its role in protecting telomeres, the CST complex also contributes to protecting DSBs from end resection. Using CRISPR/SpCas9-based loss-of-function screens, Barazas et al. show that loss of the CTC1-STN1-TEN1 (CST) complex promotes PARP inhibitor resistance in BRCA1-deficient cells. Mechanistically, the CST complex maintains double-strand break end stability in addition to its role in protecting telomeric ends

Developing a minimum data set, known as a core outcome set, for future infertility research

Background: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions, and outcome reporting bias, make the results of infertility research difficult to interpret. Objectives: To develop a core outcome set to standardise outcome selection, collection, and reporting across future randomized controlled trials and systematic reviews evaluating potential treatments for infertility. Methods: Healthcare professionals, researchers, and people with fertility problems were brought together in an open and transparent process using formal consensus science methods including a three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries) (1). Results: The core outcome set consists of: (1) viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin, and higher multiple pregnancies); (2) pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy); (3) live birth; (4) gestational age at delivery; (5) birth weight; (6) neonatal mortality; and (7) major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Conclusions: Embedding the core outcome set within randomized controlled trials and systematic reviews should ensure the comprehensive selection, collection, and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including Cochrane Gynaecology and Fertility Group, Fertility and Sterility, and Human Reproduction, have committed to implementing this core outcome set