Population screening shows risk of inherited cancer and familial hypercholesterolemia in Oregon.

The Healthy Oregon Project (HOP) is a statewide effort that aims to build a large research repository and influence the health of Oregonians through providing no-cost genetic screening to participants for a next-generation sequencing 32-gene panel comprising genes related to inherited cancers and familial hypercholesterolemia. This type of unbiased population screening can detect at-risk individuals who may otherwise be missed by conventional medical approaches. However, challenges exist for this type of high-throughput testing in an academic setting, including developing a low-cost high-efficiency test and scaling up the clinical laboratory for processing large numbers of samples. Modifications to our academic clinical laboratory including efficient test design, robotics, and a streamlined analysis approach increased our ability to test more than 1,000 samples per month for HOP using only one dedicated HOP laboratory technologist. Additionally, enrollment using a HIPAA-compliant smartphone app and sample collection using mouthwash increased efficiency and reduced cost. Here, we present our experience three years into HOP and discuss the lessons learned, including our successes, challenges, opportunities, and future directions, as well as the genetic screening results for the first 13,670 participants tested. Overall, we have identified 730 pathogenic/likely pathogenic variants in 710 participants in 24 of the 32 genes on the panel. The carrier rate for pathogenic/likely pathogenic variants in the inherited cancer genes on the panel for an unselected population was 5.0% and for familial hypercholesterolemia was 0.3%. Our laboratory experience described here may provide a useful model for population screening projects in other states.

Implementation science and the Health Resources and Services Administration's Ryan White HIV/AIDS Program's work towards ending the HIV epidemic in the United States.

Demetrios Psihopaidas and co-authors discuss the implementation science framework of an HIV/AIDS program in the United States.

Public perception of predictive cancer genetic testing and research in Oregon.

The potential for using widespread genetic testing to inform health care has become a viable option, particularly for heritable cancers. Yet, little is known about how to effectively communicate the benefits and risks of both personal genetic testing and participation in biorepositories that aid scientific advancements. Nationwide efforts are engaging communities in large genetic studies to better estimate the population-wide prevalence of heritable cancers but have been met with hesitance or declination to participate in some communities. To successfully engage an Oregon population in longitudinal research that includes predictive genetic testing for pathogenic or likely pathogenic variants associated with an increased risk for cancer, researchers conducted 35 focus groups (two of which were held in Spanish) in 24 of Oregon's 36 counties to better understand knowledge and attitudes related to genetic testing and willingness to participate in longitudinal genetic research. A total of 203 adults (mean = 45.6 years; range 18-88), representing a range of education levels and prior knowledge of genetic research, participated in the focus groups. The majority (85%) of participants reported personal or family diagnoses of cancer (e.g., self, family, friends). A majority (87%) also reported a strong interest in cancer genetic testing and receiving genetic information about themselves. Nearly all focus groups (94%, 33 of 35 sites) included participant discussion citing their families (e.g., children, close relatives, and extended family members) as key motivators for participation in genetic research. For example, participants reported interest in increasing personal knowledge about their own and their families' cancer risks in order to respond proactively, if a pathogenic variant was found. While most focus groups (94%, 33 of 35 sites) included participant discussion describing barriers to predictive genetic, testing such as concerns about outcomes, the desire to learn about health risks in oneself mitigated or outweighed those fears for many participants. Other commonly reported concerns were related to potential mistrust of insurance companies, researchers, or institutions, or lack of knowledge about genetics, genetic testing, or genetic research. Participants, particularly in rural areas, highlighted critical factors for research recruitment, such as trust, personal interaction, public education about genetic research, and clear communication about study goals and processes. Our statewide findings reflect that public interest in predictive cancer genetic testing and cancer genetic research can surpass lack of knowledge of the complex topics, particularly when benefits for self and family are emphasized and when study considerations are well articulated.

Target engagement and cellular fate of otelixizumab: a repeat dose escalation study of an anti-CD3ε mAb in new-onset type 1 diabetes mellitus patients.

AIMS: This paper describes the pharmacological findings from a study where otelixizumab, an anti-CD3ɛ mAb, was dosed in new onset Type 1 diabetes mellitus (NOT1DM) patients. This is the first time that the full dose-response of an anti-CD3ɛ mAb has been investigated in the clinic. The data have been validated using a previously developed pharmacokinetic/pharmacodynamic (PK/PD) model of otelixizumab to simulate the interplay between drug administration, CD3ɛ target engagement and downmodulation. METHODS: Patients were randomized to control or active treatment with otelixizumab (1:4), administered via infusion over 6 days, in a dose-ascending study consisted of three cohorts (n = 10 per cohort) at doses of 9, 18 or 27 mg respectively. The study allowed quantification of otelixizumab PK, CD3ɛ target engagement and its pharmacodynamic effect (CD3ε/TCR modulation on circulating T lymphocytes). RESULTS: Otelixizumab concentrations increased and averaged to 364.09 (54.3), 1625.55 (72.5) and 2781.35 (28.0) ng ml-1 (Geom.mean, %CV) at the 9, 18 and 27 mg dose respectively. CD3ɛ target engagement was found to be rapid (within the first 30 min), leading to a receptor occupancy of ~60% within 6 h of dosing in all three doses. A dose-response relationship was observed with the two highest doses achieving a ~90% target engagement and consequential CD3ɛ/TCR downmodulation by Day 6. CONCLUSIONS: Data from this study revealed maximum target engagement and CD3ɛ/TCR modulation is achieved at doses of 18, 27 mg of otelixizumab. These findings can be useful in guiding dose selection in clinical trials with anti-CD3ɛ mAbs.

Anti-IL-7 receptor α monoclonal antibody (GSK2618960) in healthy subjects - a randomized, double-blind, placebo-controlled study.

AIM: Interleukin (IL)-7 signalling modulates T cell activity and is implicated in numerous autoimmune diseases. The present study investigated the safety, pharmacokinetics, target engagement, pharmacodynamics and immunogenicity of GSK2618960, an IL-7 receptor-α subunit (CD127) monoclonal antibody. METHODS: A double-blind (sponsor-unblind) study of a single intravenous infusion of either GSK2618960 (0.6 mg kg-1 or 2.0 mg kg-1 ) or placebo was carried out in 18 healthy subjects over 24 weeks. RESULTS: GSK2618960 was well tolerated; there were no serious or significant adverse events. The observed half-life was 5 (±1) days (2.0 mg kg-1 ), with nonlinear pharmacokinetics. Full receptor occupancy (>95%) was observed until day 8 (0.6 mg kg-1 ) and day 22 (2.0 mg kg-1 ). Maximal inhibition of IL-7-mediated signal transducer and activator of transcription 5 (STAT5) phosphorylation was observed in 5/6 subjects until day 22 (2.0 mg kg-1 ). Mean circulating IL-7 and soluble receptor (CD127) levels were increased above baseline during days 2 and 15 (0.6 mg kg-1 ) and days 2 and 22 (2.0 mg kg-1 ). No meaningful changes were observed in absolute numbers or proportions of immune cell populations or inflammatory cytokine profiles (IL-6, tumour necrosis factor-α, interferon-γ, IL-2). Persistent antidrug antibodies (ADAs) were detected in 5/6 subjects administered a dose of 0.6 mg kg-1 (neutralizing in 2/6) and in 6/6 subjects administered 2.0 mg kg-1 (neutralizing in 5/6). CONCLUSION: GSK2618960 was well tolerated and blocked IL-7 receptor signalling upon full target engagement. Although there was no discernible impact on peripheral T cell subsets in healthy subjects, GSK2618960 may effectively modulate the autoinflammatory activity of pathogenic T cells in diseased tissue. A relatively short half-life is likely the result of target-mediated rather than ADA-mediated clearance.

Risk factors for negative experiences during psychotherapy.

BACKGROUND: It is estimated that between 3% and 15% of patients have a negative experience of psychotherapy, but little is understood about this. AIMS: The aim of this study was to investigate the factors associated with patients' negative therapy experiences. METHOD: The data comprised 185 patient and 304 therapist questionnaires, 20 patient and 20 therapist interviews. Patients reported on an unhelpful or harmful experience of therapy, and therapists on a therapy where they thought the patient they were working with had a poor or harmful experience. These were transcribed and analysed using thematic analysis. RESULTS: There was a Lack of fit between Patient needs, Therapist skills, and Service structures. This could result in Fault Lines, a tension between Safety and containment and Power and control. This tension led to Strain and Poor Engagement, which led to Consequences following the negative therapy experience. CONCLUSIONS: Patients require clear information, choice, involvement in decision-making, explicit contracting and clarity about sessions and progress. Opportunities for patient feedback should be the norm, where the therapist and service are vigilant for signs of deterioration and solutions considered. Clinical and methodological significance of this article: Estimates of "unwanted effects," including long-lasting effects, of psychotherapy have ranged from 3% to 15%. Few empirical studies have been conducted in this area. This study aimed to address this gap and provide clinicians with a model of risk factors for negative therapy effects. The findings of this study indicate the importance of providing patients with a supportive service structure that offers clear information, choice and involvement in decision-making. Explicit contracting at the beginning of therapy and clarity about sessions and progress are also important in managing patient expectations throughout. Opportunities for patient feedback should be provided.

Water T2 as an early, global and practical biomarker for metabolic syndrome: an observational cross-sectional study.

BACKGROUND: Metabolic syndrome (MetS) is a highly prevalent condition that identifies individuals at risk for type 2 diabetes mellitus and atherosclerotic cardiovascular disease. Prevention of these diseases relies on early detection and intervention in order to preserve pancreatic ß-cells and arterial wall integrity. Yet, the clinical criteria for MetS are insensitive to the early-stage insulin resistance, inflammation, cholesterol and clotting factor abnormalities that characterize the progression toward type 2 diabetes and atherosclerosis. Here we report the discovery and initial characterization of an atypical new biomarker that detects these early conditions with just one measurement. METHODS: Water T2, measured in a few minutes using benchtop nuclear magnetic resonance relaxometry, is exquisitely sensitive to metabolic shifts in the blood proteome. In an observational cross-sectional study of 72 non-diabetic human subjects, the association of plasma and serum water T2 values with over 130 blood biomarkers was analyzed using bivariate, multivariate and logistic regression. RESULTS: Plasma and serum water T2 exhibited strong bivariate correlations with markers of insulin, lipids, inflammation, coagulation and electrolyte balance. After correcting for confounders, low water T2 values were independently and additively associated with fasting hyperinsulinemia, dyslipidemia and subclinical inflammation. Plasma water T2 exhibited 100% sensitivity and 87% specificity for detecting early insulin resistance in normoglycemic subjects, as defined by the McAuley Index. Sixteen normoglycemic subjects with early metabolic abnormalities (22% of the study population) were identified by low water T2 values. Thirteen of the 16 did not meet the harmonized clinical criteria for metabolic syndrome and would have been missed by conventional screening for diabetes risk. Low water T2 values were associated with increases in the mean concentrations of 6 of the 16 most abundant acute phase proteins and lipoproteins in plasma. CONCLUSIONS: Water T2 detects a constellation of early abnormalities associated with metabolic syndrome, providing a global view of an individual's metabolic health. It circumvents the pitfalls associated with fasting glucose and hemoglobin A1c and the limitations of the current clinical criteria for metabolic syndrome. Water T2 shows promise as an early, global and practical screening tool for the identification of individuals at risk for diabetes and atherosclerosis.

Anchored pseudo-de novo assembly of human genomes identifies extensive sequence variation from unmapped sequence reads.

The human genome reference (HGR) completion marked the genomics era beginning, yet despite its utility universal application is limited by the small number of individuals used in its development. This is highlighted by the presence of high-quality sequence reads failing to map within the HGR. Sequences failing to map generally represent 2-5 % of total reads, which may harbor regions that would enhance our understanding of population variation, evolution, and disease. Alternatively, complete de novo assemblies can be created, but these effectively ignore the groundwork of the HGR. In an effort to find a middle ground, we developed a bioinformatic pipeline that maps paired-end reads to the HGR as separate single reads, exports unmappable reads, de novo assembles these reads per individual and then combines assemblies into a secondary reference assembly used for comparative analysis. Using 45 diverse 1000 Genomes Project individuals, we identified 351,361 contigs covering 195.5 Mb of sequence unincorporated in GRCh38. 30,879 contigs are represented in multiple individuals with ~40 % showing high sequence complexity. Genomic coordinates were generated for 99.9 %, with 52.5 % exhibiting high-quality mapping scores. Comparative genomic analyses with archaic humans and primates revealed significant sequence alignments and comparisons with model organism RefSeq gene datasets identified novel human genes. If incorporated, these sequences will expand the HGR, but more importantly our data highlight that with this method low coverage (~10-20×) next-generation sequencing can still be used to identify novel unmapped sequences to explore biological functions contributing to human phenotypic variation, disease and functionality for personal genomic medicine.

A self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy: a randomised controlled trial (the SELF study).

OBJECTIVES: To evaluate the clinical effectiveness of a self-managed single exercise programme versus usual physiotherapy treatment for rotator cuff tendinopathy. DESIGN: Multi-centre pragmatic unblinded parallel group randomised controlled trial. SETTING: UK National Health Service. PARTICIPANTS: Patients with a clinical diagnosis of rotator cuff tendinopathy. INTERVENTIONS: The intervention was a programme of self-managed exercise prescribed by a physiotherapist in relation to the most symptomatic shoulder movement. The control group received usual physiotherapy treatment. MAIN OUTCOME MEASURES: The primary outcome measure was the Shoulder Pain & Disability Index (SPADI) at three months. Secondary outcomes included the SPADI at six and twelve months. RESULTS: A total of 86 patients (self-managed loaded exercise n=42; usual physiotherapy n=44) were randomised. Twenty-six patients were excluded from the analysis because of lack of primary outcome data at the 3 months follow-up, leaving 60 (n=27; n=33) patients for intention to treat analysis. For the primary outcome, the mean SPADI score at three months was 32.4 (SD 20.2) for the self-managed group, and 30.7 (SD 19.7) for the usual physiotherapy treatment group; mean difference adjusted for baseline score: 3.2 (95% Confidence interval -6.0 to +12.4 P = 0.49).By six and twelve months there remained no significant difference between the groups. CONCLUSIONS: This study does not provide sufficient evidence of superiority of one intervention over the other in the short-, mid- or long-term and hence a self-management programme based around a single exercise appears comparable to usual physiotherapy treatment.

Cross-species array comparative genomic hybridization identifies novel oncogenic events in zebrafish and human embryonal rhabdomyosarcoma.

Human cancer genomes are highly complex, making it challenging to identify specific drivers of cancer growth, progression, and tumor maintenance. To bypass this obstacle, we have applied array comparative genomic hybridization (array CGH) to zebrafish embryonal rhabdomyosaroma (ERMS) and utilized cross-species comparison to rapidly identify genomic copy number aberrations and novel candidate oncogenes in human disease. Zebrafish ERMS contain small, focal regions of low-copy amplification. These same regions were commonly amplified in human disease. For example, 16 of 19 chromosomal gains identified in zebrafish ERMS also exhibited focal, low-copy gains in human disease. Genes found in amplified genomic regions were assessed for functional roles in promoting continued tumor growth in human and zebrafish ERMS--identifying critical genes associated with tumor maintenance. Knockdown studies identified important roles for Cyclin D2 (CCND2), Homeobox Protein C6 (HOXC6) and PlexinA1 (PLXNA1) in human ERMS cell proliferation. PLXNA1 knockdown also enhanced differentiation, reduced migration, and altered anchorage-independent growth. By contrast, chemical inhibition of vascular endothelial growth factor (VEGF) signaling reduced angiogenesis and tumor size in ERMS-bearing zebrafish. Importantly, VEGFA expression correlated with poor clinical outcome in patients with ERMS, implicating inhibitors of the VEGF pathway as a promising therapy for improving patient survival. Our results demonstrate the utility of array CGH and cross-species comparisons to identify candidate oncogenes essential for the pathogenesis of human cancer.

Phosphodiesterase-8A binds to and regulates Raf-1 kinase.

V-raf-1 murine leukemia viral oncogene homolog 1 (Raf-1) is a key activator of the ERK pathway and is a target for cross-regulation of this pathway by the cAMP signaling system. The cAMP-activated protein kinase, PKA, inhibits Raf-1 by phosphorylation on S259. Here, we show that the cAMP-degrading phosphodiesterase-8A (PDE8A) associates with Raf-1 to protect it from inhibitory phosphorylation by PKA, thereby enhancing Raf-1's ability to stimulate ERK signaling. PDE8A binds to Raf-1 with high (picomolar) affinity. Mapping of the interaction domain on PDE8A using peptide array technology identified amino acids 454-465 as the main binding site, which could be disrupted by mutation. A cell-permeable peptide corresponding to this region disrupted the PDE8A/Raf-1 interaction in cells, thereby reducing ERK activation and the cellular response to EGF. Overexpression of a catalytically inactive PDE8A in cells displayed a dominant negative phenotype on ERK activation. These effects were recapitulated at the organism level in genetically modified (PDE8A(-/-)) mice. Similarly, PDE8 deletion in Drosophila melanogaster reduced basal ERK activation and sensitized flies to stress-induced death. We propose that PDE8A is a physiological regulator of Raf-1 signaling in some cells.

Use of the methacetin breath test to classify the risk of cirrhotic complications and mortality in patients evaluated/listed for liver transplantation.

BACKGROUND & AIMS: The MELD score predicts short-term mortality in patients with cirrhosis; however, some patients with low scores develop complications and die unexpectedly. Consequently, we evaluated the diagnostic accuracy of the methacetin breath test (MBT), an assay of liver metabolic function, and the MELD score, to predict the risk of complications of cirrhosis and liver-related death. METHODS: One hundred sixty-five patients with cirrhosis received oral (13)C-methacetin; (13)CO2 was measured in expired breath (BreathID; Exalenz). The cumulative percent dose recovery of (13)CO2 at 20 min with a threshold of ⩽0.55% (high-risk) and >0.55% (low risk) most accurately predicted liver-related death and the risk of cirrhotic complications within one year. MELD thresholds of ⩾15 and ⩾19 were also examined to predict the same endpoints. RESULTS: Dose recovery ⩽0.55% and MELD ⩾19 both predicted liver-related death (HR 12.6 [95% CI 1.6-98.3]; p=0.016, and HR 5.5 [1.6-18.9]; p=0.007, respectively); MELD ⩾15 did not. Dose recovery ⩽0.55% (HR 1.9 [1.1-3.2]; p=0.03) also predicted the risk of ⩾1 complication(s), and was particularly able to foretell the risk of development/exacerbation of ascites (HR 4.7 [1.8-11.9]; p=0.001), which was not achieved by either MELD threshold. Finally, in patients with MELD <19, dose recovery ⩽0.55% predicted the risk of death (p=0.017), development of ⩾1 cirrhotic complication(s) (p=0.062), and development/exacerbation of ascites (p=0.0009). CONCLUSIONS: In this pilot study, methacetin breath testing predicted the risk of liver-related death and development/exacerbation of ascites more accurately than MELD ⩾15 or ⩾19. In patients with low MELD (<19points), MBT may be useful to identify patients in whom the frequency of clinical observation should be intensified.

Sleep deprivation impairs cAMP signalling in the hippocampus.

Millions of people regularly obtain insufficient sleep. Given the effect of sleep deprivation on our lives, understanding the cellular and molecular pathways affected by sleep deprivation is clearly of social and clinical importance. One of the major effects of sleep deprivation on the brain is to produce memory deficits in learning models that are dependent on the hippocampus. Here we have identified a molecular mechanism by which brief sleep deprivation alters hippocampal function. Sleep deprivation selectively impaired 3', 5'-cyclic AMP (cAMP)- and protein kinase A (PKA)-dependent forms of synaptic plasticity in the mouse hippocampus, reduced cAMP signalling, and increased activity and protein levels of phosphodiesterase 4 (PDE4), an enzyme that degrades cAMP. Treatment of mice with phosphodiesterase inhibitors rescued the sleep-deprivation-induced deficits in cAMP signalling, synaptic plasticity and hippocampus-dependent memory. These findings demonstrate that brief sleep deprivation disrupts hippocampal function by interfering with cAMP signalling through increased PDE4 activity. Thus, drugs that enhance cAMP signalling may provide a new therapeutic approach to counteract the cognitive effects of sleep deprivation.

Development and validation of a system of assimilation indices: A mixed method approach to understand change in psychotherapy.

OBJECTIVES: Assimilation is an important process in understanding change in psychotherapy. Similar to other psychological processes, assimilation may be traceable in the speech of clients by attending to its signs or indices. In the present research, we aimed to build a system of indices of assimilation. DESIGN AND METHODS: This research follows a mixed method design. The indices were derived through qualitative analysis, using grounded theory. Subsequently, the indices were adjusted quantitatively and applied to 30 single psychotherapy sessions of adult clients with depression and 11 therapists. Forty-two indices were found and grouped into the following five process categories of assimilation: external distress, pain, noticing, decentring and action. RESULTS: The indices showed good inter-rater reliability and internal consistency. Except for noticing, all process categories correlated significantly with each other according to conceptual proximity. The system of indices also showed convergent validity with an existing coding system of assimilation for two process categories. CONCLUSIONS: The results suggest that the system of indices is a useful approach for understanding assimilation. The consideration of assimilation in a continuous fashion through sub-processes may help to extend our knowledge of this process and provide a tool for clinical practice. PRACTITIONER POINTS: Assimilation is an important process in understanding change in psychotherapy in the sense that it takes into account insight and action-related processes. Clients convey in their speech signs or indices of the assimilation process which can be observed both in the style and content of their utterances. Using these indices, therapists can continuously assess assimilation and use this information in choosing interventions. Limitations: This study follows a cross-sectional design and does not allow consideration of the predictive value of the indices. The outcome of the therapy was not taken into account, which restricts validity considerations to the comparison with an existing instrument and the observation of the relation between sub-processes of assimilation.

Extensive genetic diversity and substructuring among zebrafish strains revealed through copy number variant analysis.

Copy number variants (CNVs) represent a substantial source of genomic variation in vertebrates and have been associated with numerous human diseases. Despite this, the extent of CNVs in the zebrafish, an important model for human disease, remains unknown. Using 80 zebrafish genomes, representing three commonly used laboratory strains and one native population, we constructed a genome-wide, high-resolution CNV map for the zebrafish comprising 6,080 CNV elements and encompassing 14.6% of the zebrafish reference genome. This amount of copy number variation is four times that previously observed in other vertebrates, including humans. Moreover, 69% of the CNV elements exhibited strain specificity, with the highest number observed for Tubingen. This variation likely arose, in part, from Tubingen's large founding size and composite population origin. Additional population genetic studies also provided important insight into the origins and substructure of these commonly used laboratory strains. This extensive variation among and within zebrafish strains may have functional effects that impact phenotype and, if not properly addressed, such extensive levels of germ-line variation and population substructure in this commonly used model organism can potentially confound studies intended for translation to human diseases.

Measuring the impact of scientific publications and publication extenders: examples of novel approaches.

Different stakeholders, such as authors, research institutions, and healthcare professionals (HCPs) may determine the impact of peer-reviewed publications in different ways. Commonly-used measures of research impact, such as the Journal Impact Factor or the H-index, are not designed to evaluate the impact of individual articles. They are heavily dependent on citations, and therefore only measure impact of the overall journal or researcher respectively, taking months or years to accrue. The past decade has seen the development of article-level metrics (ALMs), that measure the online attention received by an individual publication in contexts including social media platforms, news media, citation activity, and policy and patent citations. These new tools can complement traditional bibliometric data and provide a more holistic evaluation of the impact of a publication. This commentary discusses the need for ALMs, and summarizes several examples - PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. We also discuss how metrics may be used to evaluate the value of "publication extenders" - educational microcontent such as animations, videos and plain-language summaries that are often hosted on HCP education platforms. Publication extenders adapt a publication's key data to audience needs and thereby extend a publication's reach. These new approaches have the potential to address the limitations of traditional metrics, but the diversity of new metrics requires that users have a keen understanding of which forms of impact are relevant to a specific publication and select and monitor ALMs accordingly.

Different readers have different ways of deciding how important scientific articles are. The usual methods used to measure the impact of research, like the Journal Impact Factor or the H-index, are not meant to measure this for individual articles. These methods mainly look at how many times the articles are mentioned by others, and it can take a long time to see the impact.But in the past ten years, new tools called article-level metrics (ALMs) have been created. These tools measure how much attention an article gets online, like on social media, in the news, or when other researchers talk about it. ALMs are better at explaining how important a specific article is. They can work together with the usual methods to measure impact.This paper talks about why ALMs are important and gives examples of these tools, like PlumX Metrics, Altmetric, the Better Article Metrics score, the EMPIRE Index, and scite. It also explains how these tools can help us see the value of animations, videos, or summaries in simple language. These make it easier for more people to understand and learn from the articles.These new ways of measuring impact can help us see how important articles are in a more complete way. But because there are many different ways to measure this, it's important for users to understand which methods are relevant for a specific article and keep track of them.

Novel recruitment approaches and operational results for a statewide population Cohort for cancer research: The Healthy Oregon Project.

Background: Cancer health research relies on large-scale cohorts to derive generalizable results for different populations. While traditional epidemiological cohorts often use costly random sampling or self-motivated, preselected groups, a shift toward health system-based cohorts has emerged. However, such cohorts depend on participants remaining within a single system. Recent consumer engagement models using smartphone-based communication, driving projects, and social media have begun to upend these paradigms. Methods: We initiated the Healthy Oregon Project (HOP) to support basic and clinical cancer research. HOP study employs a novel, cost-effective remote recruitment approach to effectively establish a large-scale cohort for population-based studies. The recruitment leverages the unique email account, the HOP website, and social media platforms to direct smartphone users to the study app, which facilitates saliva sample collection and survey administration. Monthly newsletters further facilitate engagement and outreach to broader communities. Results: By the end of 2022, the HOP has enrolled approximately 35,000 participants aged 18-100 years (median = 44.2 years), comprising more than 1% of the Oregon adult population. Among those who have app access, ∼87% provided consent to genetic screening. The HOP monthly email newsletters have an average open rate of 38%. Efforts continue to be made to improve survey response rates. Conclusion: This study underscores the efficacy of remote recruitment approaches in establishing large-scale cohorts for population-based cancer studies. The implementation of the study facilitates the collection of extensive survey and biological data into a repository that can be broadly shared and supports collaborative clinical and translational research.

Cost-effectiveness of an improving access to psychological therapies service.

BACKGROUND: Effective psychological therapies have been recommended for common mental health problems, such as depression and anxiety, but provision has been poor. Improving Access to Psychological Therapies (IAPT) may provide a cost-effective solution to this problem. AIMS: To determine the cost-effectiveness of IAPT at the Doncaster demonstration site (2007-2009). METHOD: An economic evaluation comparing costs and health outcomes for patients at the IAPT demonstration site with those for comparator sites, including a separate assessment of lost productivity. Sensitivity analyses were undertaken. RESULTS: The IAPT site had higher service costs and was associated with small additional gains in quality-adjusted life-years (QALYs) compared with its comparator sites, resulting in a cost per QALY gained of £29 500 using the Short Form (SF-6D). Sensitivity analysis using predicted EQ-5D scores lowered this to £16 857. Costs per reliable and clinically significant (RCS) improvement were £9440 per participant. CONCLUSIONS: Improving Access to Psychological Therapies provided a service that was probably cost-effective within the usual National Institute for Health and Clinical Excellence (NICE) threshold range of £20 000-30 000, but there was considerable uncertainty surrounding the costs and outcome differences.

The Community Research Liaison Model: Facilitating community-engaged research.

The Community Research Liaison Model (CRLM) is a novel model to facilitate community-engaged research (CEnR) and community-academic research partnerships focused on health priorities identified by the community. This model, informed by the Principles of Community Engagement, builds trust among rural communities and expands capacity for community and investigator-initiated research. We describe the CRLM development process and how it is operationalized today. We followed a multi-phase process to design and implement a community engagement model that could be replicated. The resulting CRLM moves community-academic research collaborations from objectives to outputs using a conceptual framework that specifies our guiding principles, objectives, and actions to facilitate the objectives (i.e., capacity, motivations, and partners), and outputs. The CRLM has been fully implemented across Oregon. Six Community Research Liaisons collectively support 18 predominantly rural Oregon counties. Since 2017, the liaison team has engaged with communities on nearly 300 community projects. The CRLM has been successful in facilitating CEnR and community-academic research partnerships. The model has always existed on a dynamic foundation and continues to be responsive to the lessons learned by the community and researchers. The model is expanding across Oregon as an equitable approach to addressing health disparities across the state.