Goal-directed versus outcome-based financial incentives for weight loss among low-income patients with obesity: rationale and design of the Financial Incentives foR Weight Reduction (FIReWoRk) randomised controlled trial.

IntroductionObesity is a major public health challenge and exacerbates economic disparities through employment discrimination and increased personal health expenditures. Financial incentives for weight management may intensify individuals' utilisation of evidence-based behavioural strategies while addressing obesity-related economic disparities in low-income populations. Trials have focused on testing incentives contingent on achieving weight loss outcomes. However, based on social cognitive and self-determination theories, providing incentives for achieving intermediate behavioural goals may be more sustainable than incentivising outcomes if they enhance an individual's skills and self-efficacy for maintaining long-term weight loss. The objective of this paper is to describe the rationale and design of the Financial Incentives foR Weight Reduction study, a randomised controlled trial to test the comparative effectiveness and cost-effectiveness of two financial incentive strategies for weight loss (goal directed vs outcome based) among low-income adults with obesity, as well as compared with the provision of health behaviour change resources alone.Methods and analysisWe are recruiting 795 adults, aged 18-70 years with a body mass index ≥30 kg/m2, from three primary care clinics serving residents of socioeconomically disadvantaged neighbourhoods in New York City and Los Angeles. All participants receive a 1-year commercial weight loss programme membership, self-monitoring tools (bathroom scale, food journal and Fitbit Alta HR), health education and monthly check-in visits. In addition to these resources, those in the two intervention groups can earn up to $750 over 6 months for: (1) participating in an intensive weight management programme, self-monitoring weight and diet and meeting physical activity guidelines (goal-directed arm); or (2) a ≥1.5% to ≥5% reduction in baseline weight (outcome-based arm). To maximise incentive efficacy, we incorporate concepts from behavioural economics, including immediacy of payments and framing feedback to elicit regret aversion. We will use generalised mixed effect models for repeated measures to examine intervention effects on weight at 6, 9 and 12 months.Ethics and disseminationHuman research protection committees at New York University School of Medicine, University of California Los Angeles (UCLA) David Geffen School of Medicine and Olive-View-UCLA Medical Center granted ethics approval. We will disseminate the results of this research via peer-reviewed publications, conference presentations and meetings with stakeholders.Trial registration numberNCT03157713

The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide

Background: The amyloid $\beta$-protein (A$\beta$) is believed to be the key mediator of Alzheimer's disease (AD) pathology. A$\beta$ is most often characterized as an incidental catabolic byproduct that lacks a normal physiological role. However, A$\beta$ has been shown to be a specific ligand for a number of different receptors and other molecules, transported by complex trafficking pathways, modulated in response to a variety of environmental stressors, and able to induce pro-inflammatory activities. Methodology/Principal Findings: Here, we provide data supporting an in vivo function for A$\beta$ as an antimicrobial peptide (AMP). Experiments used established in vitro assays to compare antimicrobial activities of A$\beta$ and LL-37, an archetypical human AMP. Findings reveal that A$\beta$ exerts antimicrobial activity against eight common and clinically relevant microorganisms with a potency equivalent to, and in some cases greater than, LL-37. Furthermore, we show that AD whole brain homogenates have significantly higher antimicrobial activity than aged matched non-AD samples and that AMP action correlates with tissue A$\beta$ levels. Consistent with A$\beta$-mediated activity, the increased antimicrobial action was ablated by immunodepletion of AD brain homogenates with anti-A$\beta$ antibodies. Conclusions/Significance: Our findings suggest A$\beta$ is a hitherto unrecognized AMP that may normally function in the innate immune system. This finding stands in stark contrast to current models of A$\beta$-mediated pathology and has important implications for ongoing and future AD treatment strategies

Comprehensive analysis of Arabidopsis expression level polymorphisms with simple inheritance

In Arabidopsis thaliana, gene expression level polymorphisms (ELPs) between natural accessions that exhibit simple, single locus inheritance are promising quantitative trait locus (QTL) candidates to explain phenotypic variability. It is assumed that such ELPs overwhelmingly represent regulatory element polymorphisms. However, comprehensive genome-wide analyses linking expression level, regulatory sequence and gene structure variation are missing, preventing definite verification of this assumption. Here, we analyzed ELPs observed between the Eil-0 and Lc-0 accessions. Compared with non-variable controls, 5′ regulatory sequence variation in the corresponding genes is indeed increased. However, ∼42% of all the ELP genes also carry major transcription unit deletions in one parent as revealed by genome tiling arrays, representing a >4-fold enrichment over controls. Within the subset of ELPs with simple inheritance, this proportion is even higher and deletions are generally more severe. Similar results were obtained from analyses of the Bay-0 and Sha accessions, using alternative technical approaches. Collectively, our results suggest that drastic structural changes are a major cause for ELPs with simple inheritance, corroborating experimentally observed indel preponderance in cloned Arabidopsis QTL

HPV transcript expression affects cervical cancer response to chemoradiation

Persistent HPV infection is causative for the majority of cervical cancer cases; however, current guidelines do not require HPV testing for newly diagnosed cervical cancer. Using an institutional cohort of 88 patients with cervical cancer treated uniformly with standard-of-care chemoradiation treatment (CRT) with prospectively collected clinical outcome data, we observed that patients with cervical tumors containing HPV genotypes other than HPV 16 have worse survival outcomes after CRT compared with patients with HPV 16+ tumors, consistent with previously published studies. Using RNA sequencing analysis, we quantified viral transcription efficiency and found higher levels of E6 and the alternative transcript E6*I in cervical tumors with HPV genotypes other than HPV 16. These findings were validated using whole transcriptome data from The Cancer Genome Atlas (n = 304). For the first time to our knowledge, transcript expression level of HPV E6*I was identified as a predictive biomarker of CRT outcome in our complete institutional data set (n = 88) and within the HPV 16+ subset (n = 36). In vitro characterization of HPV E6*I and E6 overexpression revealed that both induce CRT resistance through distinct mechanisms dependent upon p53-p21. Our findings suggest that high expression of E6*I and E6 may represent novel biomarkers of CRT efficacy, and these patients may benefit from alternative treatment strategies

In vivo characterization of connective tissue remodeling using infrared photoacoustic spectra

Premature cervical remodeling is a critical precursor of spontaneous preterm birth, and the remodeling process is characterized by an increase in tissue hydration. Nevertheless, current clinical measurements of cervical remodeling are subjective and detect only late events, such as cervical effacement and dilation. Here, we present a photoacoustic endoscope that can quantify tissue hydration by measuring near-infrared cervical spectra. We quantify the water contents of tissue-mimicking hydrogel phantoms as an analog of cervical connective tissue. Applying this method to pregnant women in vivo, we observed an increase in the water content of the cervix throughout pregnancy. The application of this technique in maternal healthcare may advance our understanding of cervical remodeling and provide a sensitive method for predicting preterm birth

Decreased inappropriate shocks with new generation ICDs in children and patients with congenital heart disease

ObjectiveInappropriate implantable cardioverter defibrillator (ICD) shocks in children and patients with congenital heart disease (CHD) remain a major complication of device therapy, occurring in as many as 50% of children with ICDs. New generation devices include algorithms designed to minimize inappropriate shocks. This study aimed to evaluate the effect of new generation ICDs on the incidence of inappropriate shocks in the pediatric and CHD population.DesignRetrospective study of patients with CHD or under age 25 receiving ICDs between 2000 and 2015. New generation ICDs were defined as those with Medtronic “SmartShock” algorithms.ResultsTwo hundred eight devices were implanted in 146 patients. Rates of inappropriate shocks were similar between diagnoses (P = .71). The rate of inappropriate shock was 15% over median 5.8 years follow‐up. In the 36 patients (25%) with new generation ICDs, the rate of inappropriate shock was 6.3% over 4 years. Comparing old to new generation ICDs, freedom from first inappropriate shock was 90.6% versus 97.1% at 1 year and 80.4% versus 97.1% at 3 years (P = .01). Lead fracture was associated with having inappropriate shock (hazard ratio 8.5, P < .0001), and there was no significant difference between the device groups when lead fractures were excluded. Clinical actions were taken in 69% of patients after initial inappropriate shock (such as medication or program change, system revision, or explant). When an action was taken, subsequent inappropriate shock was reduced (5.3% vs 49.2% at 1 year; P = .002).ConclusionsPediatric and CHD patients are experiencing reduced inappropriate shocks with new generation ICD systems, though reduced lead fracture may account for this improvement. Clinical interventions after inappropriate shock favorably impact the subsequent rate of shocks once an inappropriate shock occurs.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144309/1/chd12585_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144309/2/chd12585.pd

Characteristics associated with quality of life among people with drug-resistant epilepsy

Quality of Life (QoL) is the preferred outcome in non-pharmacological trials, but there is little UK population evidence of QoL in epilepsy. In advance of evaluating an epilepsy self-management course we aimed to describe, among UK participants, what clinical and psycho-social characteristics are associated with QoL. We recruited 404 adults attending specialist clinics, with at least two seizures in the prior year and measured their self-reported seizure frequency, co-morbidity, psychological distress, social characteristics, including self-mastery and stigma, and epilepsy-specific QoL (QOLIE-31-P). Mean age was 42 years, 54% were female, and 75% white. Median time since diagnosis was 18 years, and 69% experienced ≥10 seizures in the prior year. Nearly half (46%) reported additional medical or psychiatric conditions, 54% reported current anxiety and 28% reported current depression symptoms at borderline or case level, with 63% reporting felt stigma. While a maximum QOLIE-31-P score is 100, participants’ mean score was 66, with a wide range (25–99). In order of large to small magnitude: depression, low self-mastery, anxiety, felt stigma, a history of medical and psychiatric comorbidity, low self-reported medication adherence, and greater seizure frequency were associated with low QOLIE-31-P scores. Despite specialist care, UK people with epilepsy and persistent seizures experience low QoL. If QoL is the main outcome in epilepsy trials, developing and evaluating ways to reduce psychological and social disadvantage are likely to be of primary importance. Educational courses may not change QoL, but be one component supporting self-management for people with long-term conditions, like epilepsy

State of the art conference on weight management in VA: Policy and research recommendations for advancing behavioral interventions

This article summarizes outcomes of the behavioral interventions work group for the Veterans Health Administration (VHA) State of the Art Conference (SOTA) for Weight Management. Sixteen VHA and non-VHA subject matter experts, representing clinical care delivery, research, and policy arenas, participated. The work group reviewed current evidence of efficacy, effectiveness, and implementation of behavioral interventions for weight management, participated in phone- and online-based consensus processes, generated key questions to address gaps, and attended an in-person conference in March 2016. The work group agreed that there is strong evidence for efficacy and effectiveness of core behavioral intervention components and processes, but insufficient evidence to determine the comparative effectiveness of multiple clinician delivered weight management modalities, as well as technologies that may or may not supplement clinician delivered treatments. Effective strategies for implementation of weight management services in VHA were identified. The SOTA work group’s foremost policy recommendations are to establish a system-wide culture for weight management and to identify a population-level health metric to measure the impact of weight management interventions that can be tracked and clearly communicated throughout VHA. The work group’s top research recommendation is to determine how to deploy and scale the most effective behavioral weight management interventions for Veterans