Abstract
Background
Qualitative approaches, alone or in mixed methods, are prominent within implementation science. However, traditional qualitative approaches are resource intensive, which has led ...to the development of rapid qualitative approaches. Published rapid approaches are often inductive in nature and rely on transcripts of interviews. We describe a deductive rapid analysis approach using the Consolidated Framework for Implementation Research (CFIR) that uses notes and audio recordings. This paper compares our rapid versus traditional deductive CFIR approach.
Methods
Semi-structured interviews were conducted for two cohorts of the Veterans Health Administration (VHA) Diffusion of Excellence (DoE). The CFIR guided data collection and analysis. In cohort A, we used our traditional CFIR-based deductive analysis approach (directed content analysis), where two analysts completed independent in-depth manual coding of interview transcripts using qualitative software. In cohort B, we used our new rapid CFIR-based deductive analysis approach (directed content analysis), where the primary analyst wrote detailed notes during interviews and immediately “coded” notes into a MS Excel CFIR construct by facility matrix; a secondary analyst then listened to audio recordings and edited the matrix. We tracked time for our traditional and rapid deductive CFIR approaches using a spreadsheet and captured transcription costs from invoices. We retrospectively compared our approaches in terms of effectiveness and rigor.
Results
Cohorts A and B were similar in terms of the amount of data collected. However, our rapid deductive CFIR approach required 409.5 analyst hours compared to 683 h during the traditional deductive CFIR approach. The rapid deductive approach eliminated $7250 in transcription costs. The facility-level analysis phase provided the greatest savings: 14 h/facility for the traditional analysis versus 3.92 h/facility for the rapid analysis. Data interpretation required the same number of hours for both approaches.
Conclusion
Our rapid deductive CFIR approach was less time intensive and eliminated transcription costs, yet effective in meeting evaluation objectives and establishing rigor. Researchers should consider the following when employing our approach: (1) team expertise in the CFIR and qualitative methods, (2) level of detail needed to meet project aims, (3) mode of data to analyze, and (4) advantages and disadvantages of using the CFIR.
Zika virus (ZIKV) is a re-emerging virus that has recently spread into dengue virus (DENV) endemic regions and cross-reactive antibodies (Abs) could potentially affect ZIKV pathogenesis. Using ...DENV-immune serum, it has been shown in vitro that antibody-dependent enhancement (ADE) of ZIKV infection can occur. Here we study the effects of pre-existing DENV immunity on ZIKV infection in vivo. We infect two cohorts of rhesus macaques with ZIKV; one cohort has been exposed to DENV 2.8 years earlier and a second control cohort is naïve to flaviviral infection. Our results, while confirming ADE in vitro, suggest that pre-existing DENV immunity does not result in more severe ZIKV disease. Rather our results show a reduction in the number of days of ZIKV viremia compared to naïve macaques and that the previous exposure to DENV may result in modulation of the immune response without resulting in enhancement of ZIKV pathogenesis.
Kember et al conducted a study to identify genetic factors related to alcohol consumption and alcohol use disorder (AUD). They used data from the Million Veteran Program (MVP) and found 24 ...independent variants associated with alcohol consumption and 26 independent variants associated with AUD. The authors also performed various analyses and concluded that alcohol consumption and AUD have distinct genetic architectures. The study emphasizes the importance of minimizing trait heterogeneity in future research on the genetics of alcohol use and disorder.
The four dengue virus serotypes (DENV1-4) infect several hundred million people each year living in tropical and sub-tropical regions. Clinical development of DENV vaccines is difficult because ...immunity to a single serotype increases risk of severe disease during a second infection with a new serotype. Leading vaccines are based on tetravalent formulations to induce simultaneous and balanced protective immunity to all 4 serotypes. TAK-003 is a tetravalent live attenuated dengue vaccine candidate developed by Takeda Vaccines Inc, which is currently being evaluated in phase 3 efficacy trials. Here, we use antibody depletion methods and chimeric, epitope transplant DENVs to characterize the specificity of neutralizing antibodies in dengue-naïve adults and non-human primates immunized with TAK-003. Our results demonstrate that TAK-003 induced high levels of DENV2 neutralizing antibodies that recognized unique (type-specific) epitopes on DENV2. In contrast, most vaccinated subjects developed lower levels of DENV1, DENV3 and DENV4 neutralizing antibodies that mainly targeted epitopes that were conserved (cross-reactive) between serotypes. Trial Registration: ClinicalTrials.gov NCT02425098.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dengue is a mosquito-borne flavivirus that is spreading at an unprecedented rate and has developed into a major health and economic burden in over 50 countries. Even though infected individuals ...develop potent and long-lasting serotype-specific neutralizing antibodies (Abs), the epitopes engaged by human neutralizing Abs have not been identified. Here, we demonstrate that the dengue virus (DENV)-specific serum Ab response in humans consists of a large fraction of cross-reactive, poorly neutralizing Abs and a small fraction of serotype-specific, potently inhibitory Abs. Although many mouse-generated, strongly neutralizing monoclonal antibodies (mAbs) recognize epitopes that are present on recombinant DENV envelope (E) proteins, unexpectedly, the majority of neutralizing Abs in human immune sera bound to intact virions but not to the ectodomain of purified soluble E proteins. These conclusions with polyclonal Abs were confirmed with newly generated human mAbs derived from DENV-immune individuals. Two of three strongly neutralizing human mAbs bound to E protein epitopes that were preserved on the virion but not on recombinant E (rE) protein. We propose that humans produce Abs that neutralize DENV infection by binding a complex, quaternary structure epitope that is expressed only when E proteins are assembled on a virus particle. Mapping studies indicate that this epitope has a footprint that spans adjacent E protein dimers and includes residues at the hinge between domains I and II of E protein. These results have significant implications for the DENV Ab and vaccine field.
With 2.5 billion people at risk, dengue is a major emerging disease threat and an escalating public health problem worldwide. Dengue virus causes disease ranging from a self-limiting febrile illness ...(dengue fever) to the potentially fatal dengue hemorrhagic fever/dengue shock syndrome. Severe dengue disease is associated with sub-protective levels of antibody, which exacerbate disease upon re-infection. A dengue vaccine should generate protective immunity without increasing severity of disease. To date, the determinants of vaccine-mediated protection against dengue remain unclear, and additional correlates of protection are urgently needed. Here, mice were immunized with viral replicon particles expressing the dengue envelope protein ectodomain to assess the relative contribution of humoral versus cellular immunity to protection. Vaccination with viral replicon particles provided robust protection against dengue challenge. Vaccine-induced humoral responses had the potential to either protect from or exacerbate dengue disease upon challenge, whereas cellular immune responses were beneficial. This study explores the immunological basis of protection induced by a dengue vaccine and suggests that a safe and efficient vaccine against dengue should trigger both arms of the immune system.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Stroke increases subsequent dementia risk yet there are no specific post-stroke therapies to protect cognition. Cardiorespiratory exercise is recommended for secondary prevention of stroke and may be ...neuroprotective. The Post Ischaemic Stroke Cardiovascular Exercise Study (PISCES) aims to reduce post-stroke secondary neurodegeneration and cognitive decline. During the pandemic, we pivoted to a ZOom Delivered Intervention Against Cognitive decline (ZODIAC) protocol, reducing pandemic-amplified barriers to exercise.
We present pandemic adaptions for a multicentre phase IIb assessor-blinded randomised controlled trial of ischaemic stroke survivors testing the efficacy and feasibility of an 8-week home-based exercise intervention delivered at 2 months post-stroke. We compare cardiorespiratory exercise (intervention arm) versus balance and stretching (active control arm). Participants are assessed with magnetic resonance imaging (MRI), fitness, blood, microbiome, and neuropsychological tests at three study visits: before and after the exercise intervention and at 12 months. Modifications to the original protocol include pre-exercise safety home visits, commercial delivery of exercise equipment to facilitate assessor blinding, and reconsideration of statistical plan to allow pooling of the studies. We have reduced in-person study visits from 27 to 3. Primary outcome remains between-group (intervention versus control) difference in brain volume change; secondary outcome is between-group difference in global cognitive ability to allow remote administration of a validated cognitive scale.
Remotely delivered exercise interventions reduce participant burden and may reduce barriers to recruitment. A decrease in the number of in-person study visits can be supported by greater information capture via self-reported questionnaires and phone surveys.
Prospectively ACTRN12616000942459. Registered on July 2016.
Context: The marked demographic change toward greater proportions of older people in developed nations poses significant challenges for health and social care. Several studies have demonstrated an ...association between social roles in later life and positive health and well-being outcomes. After retiring from work, people may lose roles that provide purpose and social contacts. The outcomes of interventions to promote social roles in retirement have not been systematically reviewed. Methods: We examined three research questions: (1) What kinds of intervention have been developed to promote social roles in retirement? (2) How much have they improved perceived roles? (3) Have these roles improved health or well-being? We included those studies that evaluated the provision of social roles; used a control or comparison group; targeted healthy retirement-transition adults who were living in the community; provided an abstract written in English; took place in a highly developed nation; and reported social role, health, or well-being outcomes. We searched eight electronic databases and combined the results with hand searches. Findings: Through our searches, we identified 9,062 unique publications and eleven evaluative studies of acceptable quality, which reported seven interventions that met our inclusion criteria. These interventions varied in year of inception and scope, but only two were based outside North America. The studies rarely reported the quality or meaning of roles. Only three studies used random allocation, thus limiting inferences of causality from these studies. Interventions providing explicit roles and using supportive group structures were somewhat effective in improving one or more of the following: life satisfaction, social support and activity, physical health and activity, functional health, and cognition. Conclusions: Social role interventions may improve health and well-being for people in retirement transition. Future research should improve the quality of intervention and assessment and look at which interventions are most effective and acceptable in facilitating social roles for diverse older populations.
Summary
Rhizodeposits play a key role in shaping rhizosphere microbial communities. In soybean, isoflavonoids are a key rhizodeposit component that aid in plant defense and enable symbiotic ...associations with rhizobia. However, it is uncertain if and how they influence rhizosphere microbial communities. Isoflavonoid biosynthesis was silenced via RNA interference of isoflavone synthase in soybean hairy root composite plants. Rhizosphere soil fractions tightly associated with roots were isolated, and PCR amplicons from 16S rRNA gene variable regions V1–V3 and V3–V5 from these fractions were sequenced using 454. The resulting data was resolved using MOTHUR and vegan to identify bacterial taxa and evaluate changes in rhizosphere bacterial communities. The soybean rhizosphere was enriched in Proteobacteria and Bacteroidetes, and had relatively lower levels of Actinobacteria and Acidobacteria compared with bulk soil. Isoflavonoids had a small effect on bacterial community structure, and in particular on the abundance of Xanthomonads and Comamonads. The effect of hairy root transformation on rhizosphere bacterial communities was largely similar to untransformed plant roots with approximately 74% of the bacterial families displaying similar colonization underscoring the suitability of this technique to evaluate the influence of plant roots on rhizosphere bacterial communities. However, hairy root transformation had notable influence on Sphingomonads and Acidobacteria.
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