Beyond the trial: A systematic review of real-world uptake and engagement with digital self-help interventions for depression, low mood, or anxiety

Background: Digital self-help interventions (including online or computerized programs and apps) for common mental health issues have been shown to be appealing, engaging, and efficacious in randomized controlled trials. They show potential for improving access to therapy and improving population mental health. However, their use in the real world, that is, as implemented (disseminated) outside of research settings, may differ from that reported in trials, and implementation data are seldom reported. Objective: We aimed to review peer-reviewed articles reporting user uptake and/or ongoing use, retention, or completion data (hereafter ‘usage data’ or, for brevity, ‘engagement’) from implemented pure self-help (unguided) digital interventions for depression, anxiety, or the enhancement of mood. Methods: We conducted a systematic search of the Scopus, Embase, MEDLINE, and PsychINFO databases for studies reporting user uptake and/or usage data from implemented digital self-help interventions for the treatment or prevention of depression or anxiety, or the enhancement of mood, from 2002 to 2017. Additionally, we screened the reference lists of included articles, citations of these articles, and the titles of articles published in Internet Interventions, Journal of Medical Internet Research (JMIR), and JMIR Mental Health since their inception. We extracted data indicating the number of registrations or downloads and usage of interventions. Results: After the removal of duplicates, 970 papers were identified, of which ten met the inclusion criteria. Hand-searching identified one additional article. The included articles reported on seven publically available interventions. There was little consistency in the measures reported. The number of registrants or downloads ranged widely, from eight to over 40,000 per month. From 21% to 88% of users engaged in at least minimal use (e.g. used the intervention at least once or completed one module or assessment), while 7–42% engaged in moderate use (completing between 40% and 60% of modular fixed-length programs or continuing to use apps after four weeks). Indications of completion or sustained use (completion of all modules or the last assessment or continuing to use apps after six weeks or more) varied from 0.5% to 28.6%. Conclusions: Available data suggest that uptake and engagement vary widely among the handful of implemented digital self-help apps and programs which have reported this, and that usage may vary from that reported in trials. Implementation data should be routinely gathered and reported to facilitate improved uptake and engagement, arguably among the major challenges in digital health

Natural History of Stuttering to 4 Years of Age: A Prospective Community-Based Study

These findings from a community-ascertained cohort refute long-held views suggesting that developmental stuttering is associated with a range of poorer outcomes. If anything, the reverse was true, with stuttering predicting subsequently better language,nonverbal skills, and psychosocial health-related quality of life at 4 years of age.Future research with this cohort will support a more complete longitudinal understanding of when and in whom recovery occurs. Current best practice recommends waiting for 12 monthsbefore commencing treatment, unlessthe child is distressed, there is parental concern, or the child becomes reluctant to communicate. It may be that for many children treatment could be deferred even longer. Treatment is efficacious15 but is both intensive (median of 15.4o ne-hour clinical sessions followedby 10 one-hour clinical maintenance sessions) and expensive; this "watchful waiting" recommendation would therefore help target allocation of scarce resources to the small number of children who do not resolve and experience adverse outcomes, secure in the knowledge that delaying treatment by a year or more has been shown not to compromise treatment efficac

Comparison of Measures of Ability in Adolescents with Intellectual Disability

Finding the most appropriate intelligence test for adolescents with Intellectual Disability (ID) is challenging given their limited language, attention, perceptual, and motor skills and ability to stay on task. The study compared performance of 23 adolescents with ID on the Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV), one of the most widely used intelligence tests, and three non-verbal IQ tests, the Raven's Colored Progressive Matrices (RCPM), the Test of Non-verbal Intelligence-Fourth Edition and the Wechsler Non-verbal test of Ability. Results showed that the WISC-IV Full Scale IQ raw and scaled scores were highly correlated with total scores from the three non-verbal tests, although the correlations were higher for raw scores, suggesting they may lead to better understanding of within group differences and what individuals with ID can do at the time of assessment. All participants attempted more questions on the non-verbal tests than the verbal. A preliminary analysis showed that adolescents with ID without ASD (n = 15) achieved higher scores overall than those presenting with ID+ASD (n = 8). Our findings support the view that short non-verbal tests are more likely to give a similar IQ result as obtained from the WISC-IV. In terms of the time to administer and the stress for participants, they are more appropriate for assessing adolescents with ID

Gesture production and comprehension in children with specific language impairment

Children with specific language impairment (SLI) have difficulties with spoken language. However, some recent research suggests that these impairments reflect underlying cognitive limitations. Studying gesture may inform us clinically and theoretically about the nature of the association between language and cognition. A total of 20 children with SLI and 19 typically developing (TD) peers were assessed on a novel measure of gesture production. Children were also assessed for sentence comprehension errors in a speech-gesture integration task. Children with SLI performed equally to peers on gesture production but performed less well when comprehending integrated speech and gesture. Error patterns revealed a significant group interaction: children with SLI made more gesture-based errors, whilst TD children made semantically based ones. Children with SLI accessed and produced lexically encoded gestures despite having impaired spoken vocabulary and this group also showed stronger associations between gesture and language than TD children. When SLI comprehension breaks down, gesture may be relied on over speech, whilst TD children have a preference for spoken cues. The findings suggest that for children with SLI, gesture scaffolds are still more related to language development than for TD peers who have out-grown earlier reliance on gestures. Future clinical implications may include standardized assessment of symbolic gesture and classroom based gesture support for clinical groups

Human papillomaviruses and their association with cervical disease

The overall aim of the project was to establish whether human papillomaviruses (HPV) are associated with cervical intraepithelial neoplasia (CIN) and cervical carcinoma and examine the use of HPV 16 as an indicator of cervical disease. For this purpose, a Southern blot hybridization system was developed to detect HPV DNA in cervical scrape samples. However, following the description of the polymerase chain reaction for detection of nucleic acid a PCR system for detection of HPV DNA was developed. The ability of Southern blot hybridization and PCR to detect HPV DNA in cervical scrape samples was compared to determine the most suitable method for use as a diagnostic test for HPV. The PCR method was 100,000 times more sensitive than Southern blot and was more accurate in identifying women with cervical disease. The PCR system was used to analyse cervical scrape samples from two study groups for the presence of HPV 16 DNA. The first group (Study A) consisted of 200 women from a General Practice population who were expected to have normal cervical cytology.HPV 16 was present in 17% of women with no cervical abnormalities. In those women from Study A who had cervical disease (n = 22) the prevalence of HPV 16 increased with greater severity of disease from 15.4% in those with CIN 1, 40% in those with CIN 2, to 75% of those with CIN 3. The presence of HPV 16 DNA was significantly associated with CIN 2 and 3 (p = 0.009) and was therefore useful as an indicator of severe cervical disease in this population. The ability of PCR for HPV 16 to identify women with disease was compared with that of standard cytological analysis. There was no significant difference between the two methods, although a combination of screening by cytology and PCR resulted in the identification of a higher proportion of women with disease and PCR was associated with a higher false positive rate. The second group (Study B) consisted of 200 women who had been referred to the Royal Free Hospital colposcopy clinic with a smear report suggesting mild dyskaryosis. Within this group there were 54 women who were cytologically normal, 59 women who had CIN 1 or WVI and 66 women with severe cervical disease (CIN 2 or 3). The results of Study B concurred with Study A in demonstrating an increasing prevalence of HPV 16 with greater severity of disease from 53% in women with CIN 1, 64% of women with CIN 2 to 74% of patients with CIN 3. However, the prevalence of HPV 16 in the normal women in Study B was 63%, and this high value precludes the use of HPV 16 as an indicator of severe cervical disease in this population. Duplicate analysis of each cervical scrape sample from Study A and Study B allowed the reproducibility of the HPV 16 PCR system to be determined. The false positive rate was 0.1% and the false negative rate was 0.77%. The long control region (LCR) of HPV 16 was cloned from a woman without cervical disease (CO) and a woman with CIN 3 (C3). The DNA sequence of each isolate was determined and compared with the prototype HPV 16 sequence. Nucleotide variations were evident in both isolates, but LCRC3 shared less homology with the prototype sequence than LCRCO. A single nucleotide mutation occurred within the glucocorticoid responsive element of LCRC3, which disrupts the palindrome of the protein binding domain. The level of expression from the HPV 16 LCR was determined using a chloramphenicol acetyltransferase assay and found to be 5-fold lower than that of the SV40 early promoter

A proposal for a repertoire of software testing methods

Nowadays software testing and quality assurance have a great value in software development process. Software testing does not mean a concrete discipline, it is the process of validation and verification that starts from the idea of future product and finishes at the end of product’s maintenance. The importance of software testing methods and tools that can be applied on different testing phases is highly stressed in industry. The initial objectives for this thesis were to provide a sufficient literature review on different testing phases and for each of the phases define the method that can be effectively used for improving software’s quality. Software testing phases, chosen for study are: unit testing, integration testing, functional testing, system testing, acceptance testing and usability testing. The research showed that there are many software testing methods that can be applied at different phases and in the most of the cases the choice of the method should be done depending on software type and its specification. In the thesis the problem, concerned to each of the phases was identified; the method that can help in eliminating this problem was suggested and particularly described

Acquired Nisin Resistance in Staphylococcus aureus Involves Constitutive Activation of an Intrinsic Peptide Antibiotic Detoxification Module

Resistance to the lantibiotic nisin (NIS) arises readily in Staphylococcus aureus as a consequence of mutations in the nsaS gene, which encodes the sensor kinase of the NsaRS two-component regulatory system. Here we present a series of studies to establish how these mutational changes result in reduced NIS susceptibility. Comparative transcriptomic analysis revealed upregulation of the NsaRS regulon in a NIS-resistant mutant of S. aureus versus its otherwise-isogenic progenitor, indicating that NIS resistance mutations prompt gain-of-function in NsaS. Two putative ABC transporters (BraDE and VraDE) encoded within the NsaRS regulon that have been reported to provide a degree of intrinsic protection against NIS were shown to be responsible for acquired NIS resistance; as is the case for intrinsic NIS resistance, NIS detoxification was ultimately mediated by VraDE, with BraDE participating in the signaling cascade underlying VraDE expression. Our study revealed new features of this signal transduction pathway, including that BraDE (but not VraDE) physically interacts with NsaRS. Furthermore, while BraDE has been shown to sense stimuli and signal to NsaS in a process that is contingent upon ATP hydrolysis, we established that this protein complex is also essential for onward transduction of the signal from NsaS through energy-independent means. NIS resistance in S. aureus therefore joins the small number of documented examples in which acquired antimicrobial resistance results from the unmasking of an intrinsic detoxification mechanism through gain-of-function mutation in a regulatory circuit. IMPORTANCE NIS and related bacteriocins are of interest as candidates for the treatment of human infections caused by Gram-positive pathogens such as Staphylococcus aureus. An important liability of NIS in this regard is the ease with which S. aureus acquires resistance. Here we establish that this organism naturally possesses the cellular machinery to detoxify NIS but that the ABC transporter responsible (VraDE) is not ordinarily produced to a degree sufficient to yield substantial resistance. Acquired NIS resistance mutations prompt activation of the regulatory circuit controlling expression of vraDE, thereby unmasking an intrinsic resistance determinant. Our results provide new insights into the complex mechanism by which expression of vraDE is regulated and suggest that a potential route to overcoming the resistance liability of NIS could involve chemical modification of the molecule to prevent its recognition by the VraDE transporter

Deficits in narrative abilities in child British Sign Language users with specific language impairment

This study details the first ever investigation of narrative skills in a group of 17 deaf signing children who have been diagnosed with disorders in their British Sign Language development compared with a control group of 17 deaf child signers matched for age, gender, education, quantity, and quality of language exposure and non-verbal intelligence. Children were asked to generate a narrative based on events in a language free video. Narratives were analysed for global structure, information content and local level grammatical devices, especially verb morphology. The language-impaired group produced shorter, less structured and grammatically simpler narratives than controls, with verb morphology particularly impaired. Despite major differences in how sign and spoken languages are articulated, narrative is shown to be a reliable marker of language impairment across the modality boundaries