User characteristics and outcomes from a national digital mental health service: an observational study of registrants of the Australian MindSpot Clinic.

Background:Interest is growing in digital and telehealth delivery of mental health services, but data are scarce on outcomes in routine care. The federally funded Australian MindSpot Clinic provides online and telephone psychological assessment and treatment services to Australian adults. We aimed to summarise demographic characteristics and treatment outcomes of patients registered with MindSpot over the first 7 years of clinic operation. Methods:We used an observational design to review all patients who registered for assessment with the MindSpot Clinic between Jan 1, 2013, and Dec 31, 2019. We descriptively analysed the demographics, service preferences, and baseline symptoms of patients. Among patients enrolled in a digital treatment course, we evaluated scales of depression (Patient Health Questionnaire-9 [PHQ-9]) and anxiety (Generalized Anxiety Disorder 7-Item Scale [GAD-7]), as primary measures of treatment outcome, from the screening assessment to post-treatment and a 3 month follow-up. The Kessler Psychological Distress 10-Item Plus Scale was also used to assess changes in general distress and disability, and course satisfaction was measured post-treatment. Outcomes:A total of 121 652 screening assessments were started, of which 96 018 (78·9%) were completed. The mean age of patients was 35·7 years (SD 13·8) and 88 702 (72·9%) were women. Based on available assessment data, 36 866 (34·5%) of 106 811 participants had never previously spoken to a health professional about their symptoms, and most people self-reported symptoms of anxiety (88 879 [81·9%] of 108 494) or depression (78 803 [72·6%] of 108 494), either alone or in combination, at baseline. 21 745 patients started treatment in a therapist-guided online course, of whom 14 503 (66·7%) completed treatment (≥four of five lessons). Key trends in service use included an increase in the proportion of people using MindSpot primarily for assessment and information, from 52·6% in 2013 to 66·7% in 2019, while the proportion primarily seeking online treatment decreased, from 42·6% in 2013 to 26·7% in 2019. Effect sizes and percentage changes were large for estimated mean scores on the PHQ-9 and GAD-7 from assessment to post-treatment (PHQ-9, Cohen's d effect size 1·40 [95% CI 1·37-1·43]; and GAD-7, 1·45 [1·42-1·47]) and the 3 month follow-up (PHQ-9, 1·36 [1·34-1·38]; and GAD-7, 1·42 [1·40-1·44]); proportions of patients with reliable symptom deterioration (score increase of ≥6 points [PHQ-9] or ≥5 points [GAD-7]) were low post-treatment (of 13 058 respondents, 184 [1·4%] had symptom deterioration on the PHQ-9 and 282 [2·2%] on the GAD-7); and patient satisfaction rates were high (12 452 [96·6%] of 12 895 respondents would recommend the course and 12 433 [96·7%] of 12 860 reported the course worthwhile). We also observed small improvements in disability following treatment as measured by days out of role. Interpretation:Our findings indicate improvement in psychological symptoms and positive reception among patients receiving online mental health treatment. These results support the addition of digital services such as MindSpot as a component in contemporary national mental health systems. Funding:None

Nucleotide sequence encoding the carboxyl-terminal half of apolipoprotein B from spontaneously hypercholesterolemic pigs.

Previous studies from this laboratory characterized the hypercholesterolemia of pigs with a mutant allele of apolipoprotein B (apoB), designated Lpb5. This apoB allele is associated with low density lipoprotein (LDL) particles deficient in binding to the LDL receptor. To identify potential causative mutations in Lpb5 DNA, 10.6 kb of genomic DNA, encoding the carboxyl-terminal 58% of apoB were sequenced from the Lpb5 allele and from an allele encoding phenotypically normal apoB. Comparison of the two DNA sequences revealed 33 polymorphisms, 13 of which resulted in amino acid polymorphisms. To determine whether any of the amino acids at the polymorphic positions in Lpb5-encoded apoB were unique to that isoform, those positions were sequenced in four other pig apoB alleles encoding phenotypically normal apoB. None of the amino acids were by themselves uniquely encoded by the Lpb5 allele. However, a unique haplotype consisting of Asp3164 in conjunction with Ala3447 distinguished the Lpb5-encoded apoB from all other allelic isoforms sequenced in this region. To gain insight into changes in the tertiary structure of the mutant apoB, 13C-NMR analysis of LDL reductively methylated with [13C]-formaldehyde was performed. LDL has lysine residues that titrate at pH 10.5 and others that titrate at pH 8.9. The latter residues are thought to include those involved in the interaction of LDL with the LDL receptor. LDL from Lpb5 pigs possessed a smaller proportion of lysine residues titrating at pH 8.9 than did LDL from non-Lpb5 pigs, suggesting that the Lpb5-encoded apoB is altered in a manner affecting the microenvironment of particular lysine residues

Стилистический эффект разговорной речи и его составляющие

В обучении русскому языку как иностранному на современном этапе большое внимание уделяется особенностям русской разговорной речи. Это обусловлено целым рядом причин, среди которых, на наш взгляд, можно выделить следующие: во-первых, разговорная речь всегда отличается активностью проникновения во все сферы жизнедеятельности людей и функционирует как в повседневном общении, так и в различных сферах (литературе, кино, политике и т.д.). Во-вторых, разговорная речь носит многожанровый характер, что зачастую затрудняет ее понимание иностранными студентами. В-третьих, в разговорную речь помимо слов нейтрального стиля все активнее стала проникать арготическая лексика. Именно в связи с этим особый интерес у нас вызывает разговорный стиль речи в преломлении на инофонную аудиторию

Mobilising the experiential knowledge of clinicians, patients and carers for applied health-care research

This article demonstrates the benefits of combining various types of knowledge for applied health research. Funding is available for health research despite these being ‘austere times’ for public services and international policy shifts recognise the role that patients, carers and the public can play in research. In England the National Institute for Health Research, Research Design Service (RDS) was created to ensure that the experiential knowledge of clinicians working in the National Health Service is informed by methodological expertise to achieve relevant research outcomes. The RDS also facilitates patient and public involvement in research, framed as ‘PPI’. This raises the question of how PPI impacts on research design and funding and which patients or members of the public should be involved in which aspects of research. To answer these questions we present case studies that draw on the expertise of academics, clinicians, patients and the public in applied health research. These cases demonstrate that where patients with direct experience of the condition that is to be studied are actively involved as advisers early on in applied health research, this can enhance the likelihood of successful funding applications, ethical aspects of research and the relevance of questionnaires and interventions to patients. For comparative purposes, we give an example of an unsuccessful research proposal. We contribute to theoretical development through refining the conceptualisation of PPI by unpicking the different roles that members of the public play as lay people, distinguishing this from the specific expertise that comes from direct experience of being a service user, carer or patient. We conclude that different types of knowledge are required for applied health research: methodological expertise, practice-based expertise, and the experiential expertise of patients or carers. While there are no guarantees, the scrutiny function performed by lay involvement in research funding panels can challenge the balance of power

Targeted Deletion of Kcne2 Causes Gastritis Cystica Profunda and Gastric Neoplasia

Gastric cancer is the second leading cause of cancer death worldwide. Predisposing factors include achlorhydria, Helicobacter pylori infection, oxyntic atrophy and TFF2-expressing metaplasia. In parietal cells, apical potassium channels comprising the KCNQ1 α subunit and the KCNE2 β subunit provide a K+ efflux current to facilitate gastric acid secretion by the apical H+K+ATPase. Accordingly, genetic deletion of murine Kcnq1 or Kcne2 impairs gastric acid secretion. Other evidence has suggested a role for KCNE2 in human gastric cancer cell proliferation, independent of its role in gastric acidification. Here, we demonstrate that 1-year-old Kcne2−/− mice in a pathogen-free environment all exhibit a severe gastric preneoplastic phenotype comprising gastritis cystica profunda, 6-fold increased stomach mass, increased Ki67 and nuclear Cyclin D1 expression, and TFF2- and cytokeratin 7-expressing metaplasia. Some Kcne2−/−mice also exhibited pyloric polypoid adenomas extending into the duodenum, and neoplastic invasion of thin walled vessels in the sub-mucosa. Finally, analysis of human gastric cancer tissue indicated reduced parietal cell KCNE2 expression. Together with previous findings, the results suggest KCNE2 disruption as a possible risk factor for gastric neoplasia

Influence of HAART on Alternative Reading Frame Immune Responses over the Course of HIV-1 Infection

Background: Translational errors can result in bypassing of the main viral protein reading frames and the production of alternate reading frame (ARF) or cryptic peptides. Within HIV, there are many such ARFs in both sense and the antisense directions of transcription. These ARFs have the potential to generate immunogenic peptides called cryptic epitopes (CE). Both antiretroviral drug therapy and the immune system exert a mutational pressure on HIV-1. Immune pressure exerted by ARF CD8(+) T cells on the virus has already been observed in vitro. HAART has also been described to select HIV-1 variants for drug escape mutations. Since the mutational pressure exerted on one location of the HIV-1 genome can potentially affect the 3 reading frames, we hypothesized that ARF responses would be affected by this drug pressure in vivo. Methodology/Principal findings: In this study we identified new ARFs derived from sense and antisense transcription of HIV-1. Many of these ARFs are detectable in circulating viral proteins. They are predominantly found in the HIV-1 env nucleotide region. We measured T cell responses to 199 HIV-1 CE encoded within 13 sense and 34 antisense HIV-1 ARFs. We were able to observe that these ARF responses are more frequent and of greater magnitude in chronically infected individuals compared to acutely infected patients, and in patients on HAART, the breadth of ARF responses increased. Conclusions/Significance: These results have implications for vaccine design and unveil the existence of potential new epitopes that could be included as vaccine targets.International AIDS Vaccine Initiative (IAVI

"The knight is young" at the HM Tower of London

This project consisted of an evaluation of "The Knight is Young", an exhibition by the Royal Armouries at the Tower of London. The organization wished to know how well the exhibit achieved its goals of being enjoyable and informative for all visitors, as well as people's opinions about the subject matter (children's arms and armour). This was accomplished through the use of surveys, interviews and observation of visitors. The results showed that the exhibit achieved its goals well

In situ monitoring of thin film reactions during rapid thermal annealing: Nickel silicide formation

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Genetic dissection reveals unexpected influence of beta subunits on KCNQ1 K+ channel polarized trafficking in vivo.

Targeted deletion of the Kcne2 potassium channel β subunit gene ablates gastric acid secretion and predisposes to gastric neoplasia in mice. Here, we discovered that Kcne2 deletion basolaterally reroutes the Kcnq1 α subunit in vivo in parietal cells (PCs), in which the normally apical location of the Kcnq1-Kcne2 channel facilitates its essential role in gastric acid secretion. Quantitative RT-PCR and Western blotting revealed that Kcne2 deletion remodeled fundic Kcne3 (2.9±0.8-fold mRNA increase, n=10; 5.3±0.4-fold protein increase, n=7) but not Kcne1, 4, or 5, and resulted in basolateral Kcnq1-Kcne3 complex formation in Kcne2(-/-) PCs. Concomitant targeted deletion of Kcne3 (creating Kcne2(-/-)Kcne3(-/-) mice) restored PC apical Kcnq1 localization without Kcne1, 4, or 5 remodeling (assessed by quantitative RT-PCR; n=5-10), indicating Kcne3 actively, basolaterally rerouted Kcnq1 in Kcne2(-/-) PCs. Despite this, Kcne3 deletion exacerbated gastric hyperplasia in Kcne2(-/-) mice, and both hypochlorhydria and hyperplasia in Kcne2(+/-) mice, suggesting that Kcne3 up-regulation was beneficial in Kcne2-depleted PCs. The findings reveal, in vivo, Kcne-dependent α subunit polarized trafficking and the existence and consequences of potassium channel β subunit remodeling