Search

Abstract Increasing biological nitrogen (N) fixation (BNF) in maize production could reduce the environmental impacts of N fertilizer use, but reactive N in the rhizosphere of maize limits the BNF process. Using non-transgenic methods, we developed gene-edited strains of Klebsiella variicola (Kv137-2253) and Kosakonia sacchari (Ks6-5687) bacteria optimized for root-associated BNF and ammonium excretion in N-rich conditions. The aim of this research was to elucidate the mechanism of action of these strains. We present evidence from in vitro, in planta and field experiments that confirms that our genetic remodeling strategy derepresses BNF activity in N-rich systems and increases ammonium excretion by orders of magnitude above the respective wildtype strains. BNF is demonstrated in controlled environments by the transfer of labeled 15N2 gas from the rhizosphere to the chlorophyll of inoculated maize plants. This was corroborated in several 15N isotope tracer field experiments where inoculation with the formulated, commercial-grade product derived from the gene-edited strains (PIVOT BIO PROVEN® 40) provided on average 21 kg N ha-1 to the plant by the VT-R1 growth stages. Data from small-plot and on-farm trials suggest that this technology can improve crop N status pre-flowering and has potential to mitigate the risk of yield loss associated with a reduction in synthetic N fertilizer inputs.

Abstract Background Implementation of new practices in team-based settings requires teams to work together to respond to new demands and changing expectations. However, team constructs and team-based implementation approaches have received little attention in the implementation science literature. This systematic review summarizes empirical research examining associations between teamwork and implementation outcomes when evidence-based practices and other innovations are implemented in healthcare and human service settings. Methods We searched MEDLINE, CINAHL, APA PsycINFO and ERIC for peer-reviewed empirical articles published from January 2000 to March 2022. Additional articles were identified by searches of reference lists and a cited reference search for included articles (completed in February 2023). We selected studies using quantitative, qualitative, or mixed methods to examine associations between team constructs and implementation outcomes in healthcare and human service settings. We used the Mixed Methods Appraisal Tool to assess methodological quality/risk of bias and conducted a narrative synthesis of included studies. GRADE and GRADE-CERQual were used to assess the strength of the body of evidence. Results Searches identified 10,489 results. After review, 58 articles representing 55 studies were included. Relevant studies increased over time; 71% of articles were published after 2016. We were unable to generate estimates of effects for any quantitative associations because of very limited overlap in the reported associations between team variables and implementation outcomes. Qualitative findings with high confidence were: 1) Staffing shortages and turnover hinder implementation; 2) Adaptive team functioning (i.e., positive affective states, effective behavior processes, shared cognitive states) facilitates implementation and is associated with better implementation outcomes; Problems in team functioning (i.e., negative affective states, problematic behavioral processes, lack of shared cognitive states) act as barriers to implementation and are associated with poor implementation outcomes; and 3) Open, ongoing, and effective communication within teams facilitates implementation of new practices; poor communication is a barrier. Conclusions Teamwork matters for implementation. However, both team constructs and implementation outcomes were often poorly specified, and there was little overlap of team constructs and implementation outcomes studied in quantitative studies. Greater specificity and rigor are needed to understand how teamwork influences implementation processes and outcomes. We provide recommendations for improving the conceptualization, description, assessment, analysis, and interpretation of research on teams implementing innovations. Trial registration This systematic review was registered in PROSPERO, the international prospective register of systematic reviews. Registration number: CRD42020220168.

Creative animals can flexibly respond to novel circumstances, a capacity that is closely tied to cognitive complexity. We examined the capacity of four dogs to learn to innovate actions when instructed to do so using a “create” cue. An action performed in response to this cue was considered novel if the action had not yet been offered within the current training session and was not already associated with a specific cue. The dogs were able to self-select many novel actions, similarly to what has been observed in trained dolphins. Training animals to innovate actions on cue can help reveal aspects of the cognitive processes underlying action selection, cognitive control, and behavioral flexibility. Successful learning of the “create” cue may indicate that the dogs were able to monitor their recent actions and form an abstract concept of avoiding recently performed actions. Reinforcing dogs for spontaneity may increase the range of actions that they perform within the training context. We conclude that the dogs in this study were capable of learning to innovate actions in ways that are comparable to what has been shown in dolphins. Though it is unclear how other dogs would perform at this task, our results demonstrate it is possible for dogs to learn to innovate actions on cue.

The intermediate filament vimentin is present in immune cells and is implicated in proinflammatory immune responses. Whether and how it supports antimicrobial activities of neutrophils are not well established. Here, we developed an immortalized neutrophil model to examine the requirement of vimentin. We demonstrate that vimentin restricts the production of proinflammatory cytokines and reactive oxygen species (ROS), but enhances phagocytosis and swarming. We observe that vimentin is dispensable for neutrophil extracellular trap (NET) formation, degranulation, and inflammasome activation. Moreover, gene expression analysis demonstrated that the presence of vimentin was associated with changes in expression of multiple genes required for mitochondrial function and ROS overproduction. Treatment of wild-type cells with rotenone, an inhibitor for complex I of the electron transport chain, increases the ROS levels. Likewise, treatment with mitoTEMPO, a SOD mimetic, rescues the ROS production in cells lacking vimentin. Together, these data show vimentin regulates neutrophil antimicrobial functions and alters ROS levels through regulation of mitochondrial activity.

Delivery in well-equipped facilities is important to prevent the major causes of maternal mortality. Social and structural barriers are well established across low-resource contexts; less understood is the interaction between the psychological dimensions of behavior and a pregnant woman's environment to either facilitate or hinder facility delivery. We conducted formative research applying the behavioral design approach to explore this context shaping decision-making and behavior of pregnant women, and others with influence, in Grand Cape Mount, Liberia. In-depth interviews (n = 58) were conducted in 2021 with pregnant and postpartum women, family members, facility-based providers, trained traditional midwives, community health assistants, and community leaders. Our findings highlight that while most women intend to deliver in a facility, poverty compounds difficulties at each step of the continuum of care, with the cumulative impact making facility-based delivery more difficult for lower-income, rural women to achieve. Delivering in a facility requires extensive planning and saving to overcome these difficulties and we present insights into the context contributing to a series of delays across the course of a woman's pregnancy – from initial care seeking through preparing and seeking care for childbirth, to arriving and receiving care at the facility. Our findings reveal the importance of delays earlier in pregnancy, as poor families have to weigh trade-offs of various aspects of planning and saving more carefully while also faced with chronic scarcity and competing demands for attention. Behavioral solutions that support women to make these difficult decisions and empower communities to address local challenges are still sorely needed.

Abstract Objectives: We evaluated SARS-CoV-2 anti-nucleocapsid (anti-N) seroconversion and seroreversion rates, risk factors associated with SARS-CoV-2 seroconversion, and COVID-19 risk perceptions among academic healthcare center employees in a rural state. Methods: Among employees aged ≥18 years who completed a screening survey (n = 1,377), we invited all respondents reporting previous COVID-19 (n = 85; 82 accepted) and a random selection of respondents not reporting previous COVID-19 (n = 370; 220 accepted) to participate. Participants completed surveys and provided blood samples at 3-month intervals (T0, T3, T6, T9). We used logistic regression to identify risk factors for seropositivity at T0. Results: The cohort was primarily direct patient caregivers (205/302; 67.9%), white (278/302; 92.1%), and female (212/302; 70.2%). At T0, 86/302 (28.4%) participants were seropositive. Of the seronegative participants, 6/198 (3.0%), 6/183 (3.3%), and 14/180 (7.8%) had seroconverted at T3, T6, and T9, respectively. The overall seroreversion rate was 6.98% at T9. At T0, nursing staff (odds ratio [OR], 2.37; 95% confidence interval [CI], 1.08, 5.19) and being within six feet of a non-household member outside of work (OR, 2.91; 95% CI, 1.02, 8.33) had significantly higher odds of seropositivity. Vaccination (OR, 0.05; 95% CI, 0.02, 0.12) and face mask use (OR, 0.36; 95% CI, 0.17, 0.78) were protective. Conclusions: The seroconversion and seroreversion rates were low among participants. Public health and infection prevention measures implemented early in the COVID-19 pandemic – vaccination, face mask use, and social distancing – were associated with significantly lower odds of SARS-CoV-2 seropositivity among participants.

BackgroundIllicitly manufactured fentanyls and stimulants are implicated in the escalating US mortality from drug overdose. San Francisco, California (SF) has seen declining fentanyl injection while smoking has increased. Beliefs and behaviors surrounding this development are not well understood.MethodsThe study used rapid ethnography to explore fentanyl and methamphetamine use in SF. The team conducted semi-structured interviews (n = 34) with participants recruited from syringe service programs. Video-recorded smoking sequences (n = 12), photography and daily field notes supplemented interview data.ResultsDifficulty injecting and fear of overdose motivated transitions from injecting to smoking. Fentanyl was extremely cheap-$10/gram-with variability in quality. Foil was the most commonly used smoking material but glass bubbles, bongs and dabbing devices were also popular. No reliable visible methods for determining fentanyl quality existed, however, participants could gauge potency upon inhalation, and developed techniques to regulate dosage. Several participants reported at least hourly use, some reporting one or more grams of daily fentanyl consumption. Smoking was also very social, with people sharing equipment, drugs and information. Participants raised concerns about hygiene and overdose risk to others arising from shared equipment. Reportedly potent fentanyl 'residue' accumulated on smoking materials and was commonly shared/traded/stolen or consumed accidentally with diverse preferences for its use.ConclusionOur data highlight fentanyl residue as a new overdose risk with potential mismatch between the potency of the residual drug and the recipient's tolerance. Further, large doses of fentanyl are being consumed (estimated at approximately 50 mg of pure fentanyl/day). Smoking fentanyl has potential health benefits over injecting and may be protective against overdose, but substantial uncertainty exists. However, SF overdose mortality hit a record high in 2023. Recommendations to reduce fentanyl smoking overdose risks through pacing, greater awareness of dosages consumed and checking tolerance of residue recipients are potentially viable interventions deserving further exploration.

Abstract Background Chronic pain is among the most common conditions presenting to primary care and guideline-based care faces several challenges. A novel pain management program, Video-Telecare Collaborative Pain Management (VCPM), was established to support primary care providers and meet new challenges to care presented by the COVID-19 pandemic. Methods The present single-arm feasibility study aimed to evaluate the feasibility and acceptability of VCPM and its components among U.S. veterans on long-term opioid therapy for chronic pain at ≥ 50 mg morphine equivalent daily dose (MEDD). VCPM consists of evidence-based interventions, including opioid reassessment and tapering, rotation to buprenorphine and monitoring, and encouraging behavioral pain and opioid-use disorder self-management. Results Of the 133 patients outreached for VPCM, 44 completed an initial intake (33%) and 19 attended multiple VCPM appointments (14%). Patients were generally satisfied with VCPM, virtual modalities, and provider interactions. Nearly all patients who attended multiple appointments maintained a buprenorphine switch or tapered opioids (16/19; 84%), and buprenorphine switches were generally reported as acceptable by patients. Patients completing an initial intake with VCPM had reduced morphine equivalent daily dose after three months (means = 109 mg MEDD vs 78 mg), with greater reductions among those who attended multiple appointments compared to intake only (ΔMEDD = -58.1 vs. -8.40). Finally, 29 referrals were placed for evidence-based non-pharmacologic interventions. Conclusion Pre-defined feasibility and acceptability targets for VCPM and its components were broadly met, and preliminary data are encouraging. Novel strategies to improve enrollment and engagement and future directions are discussed.

Background Driven by increased injection opioid use, rates of hospitalisation for infective endocarditis, an infection associated with injection drug use, are increasing. In the USA, 1 in 10 hospitalised patients for opioid use disorder-associated infective endocarditis (OUD-IE) die in the hospital and 1 in 20 have a patient-directed discharge. Emerging models of care reveal opportunities for healthcare systems to meet the complex care needs of these patients. We characterised promising practices of staff who care for these patients and identified areas for improvement.Methods We conducted a qualitative study with 1-hour semistructured virtual interviews between October 2021 and March 2022. Participants included 26 healthcare staff who care for patients with OUD-IE at the Hospital of the University of Pennsylvania. We used thematic analysis of interviews guided by an abductive approach. Interviews were digitally recorded and transcribed and analysed using NVivo software.Results Interviews were characterised by three major themes: (1) care rooted in interdisciplinary collaboration; (2) managing OUD and its sequelae in a setting not designed to treat OUD; and (3) clinician needs and barriers to change.Conclusions These findings highlight the facilitators of high-quality treatment for patients with OUD-IE, as well as the key areas for improvement. Findings add context to the complexity that both the healthcare staff and patients navigate during and following hospitalisation for OUD-IE. Needed changes include training staff to talk with patients about preparing for a return to drug use following hospitalisation, and changing discharge facilities’ practices that hinder access for patients with OUD-IE.

Abstract Molecular diffusive membranes play crucial roles in the field of microfluidics for biological applications e.g., 3D cell culture and biosensors. Hydrogels provide a range of benefits such as free diffusion of small molecules, cost-effectiveness, and the ability to be produced in bulk. Among various hydrogels, Pluronic F127 can be used for cell culture purposes due to its biocompatibility and flexible characteristics regarding its environment. Aqueous solutions of Pluronic F127 shows a reversible thermo-thickening property, which can be manipulated by introduction of ions. As a result, controlled diffusion of ions into the solution of Pluronic F127 can result in a controlled gel formation. In this study, the flow of immiscible solutions of Pluronic and sodium phosphate inside a Y-shaped microchannel is simulated using the level set method, and the effects of volume flow rates and temperature on the gel formation are investigated. It is indicated that the gel wall thickness can decrease by either increasing the Pluronic volume flow rate or increasing both volume flow rates while increasing the saline volume flow rate enhances the gel wall thickness. Below a critical temperature value, no gel wall is formed, and above that, a gel wall is constructed, with a thickness that increases with temperature. This setup can be used for drug screening, where gel wall provides an environment for drug-cell interactions. Article Highlights Parallel flow of Pluronic F127 and saline solutions inside a Y-shaped microchannel results in formation of a gel wall at their interface. The numerical analysis reveals the impact of each inlet flow rate and temperature on gel wall thickness and movement. The findings indicate that the gel wall has a low but steady velocity toward the saline solution. Graphical abstract

Abstract Indomethacin is used commonly in preterm neonates for the prevention of intracranial hemorrhage and closure of an abnormally open cardiac vessel. Due to biomedical advances, the infants who receive this drug in the neonatal intensive care unit setting have become younger, smaller, and less mature (more preterm) at the time of treatment. To develop a pharmacokinetics (PK) model to aid future dosing, we designed a prospective cohort study to characterize indomethacin PK in a dynamically changing patient population. A population PK base model was created using NONMEM, and a covariate model was developed in a primary development cohort and subsequently was tested for accuracy in a validation cohort. Postnatal age was a significant covariate for hepatic clearance (CLH) and renal clearance (CLR). The typical value of the total clearance (CL, the sum of CLR and CLH) was 3.09 ml/h and expressed as CL/WTmedian = 3.96 ml/h/kg, where WTmedian is the median body weight. The intersubject variability of CLR and CLH were 61% and 207%, respectively. The typical value of the volume of distribution Vp = 366 ml (Vp/WTmedian = 470 ml/kg), and its intersubject variability was 38.8%. Half‐life was 82.1 h. Compared with more mature and older preterm populations studied previously, indomethacin CL is considerably lower in this contemporary population. Model‐informed precision dosing incorporating important covariates other than weight alone offers an opportunity to individualize dosing in a susceptible patient undergoing rapid change.

To address ongoing academic achievement gap, there is a need for more school-university partnerships promoting early access to STEM education. During summer 2020, members of our institute initiated QBio-EDGE (Quantitative Biology-Empowering Diversity and Growth in Education), an outreach program for high schools in Los Angeles. In the hope of contributing to increasing diversity in academia, QBio-EDGE aims to make STEM education more accessible for students from historically excluded communities by exposing them to scientific research and diverse scientist role models. This program is led by early career researchers (ECRs), i.e., undergraduate, graduate, and postdoctoral researchers. In our first year, the outreach activities took place during virtual learning, presenting challenges and opportunities within the program development. Here, we provide a practical guide outlining our outreach efforts, key factors we considered in the program development, and hurdles we overcame. Specifically, we describe how we assembled our diverse team, how we established trusting partnerships with participating schools, and how we designed engaging student-centered, problem-based classroom modules on quantitative biology and computational methods applications to understand living systems. We also discuss the importance of increased institutional support. We hope that this may inspire researchers at all career stages to engage with local schools by participating in science outreach, specifically in quantitative and computational fields. We challenge institutions to actively strengthen these efforts.

Plain Language Summary Instances of disrespect and abuse during childbirth are prevalent around the world, particularly in low-resource settings. Few interventions have been designed and evaluated in these settings and even fewer in Southern Africa. This study aimed to understand the effects of a behaviorally informed intervention on the provision of respectful maternity care. We performed an evaluation of a health facility-based intervention, in Chipata District, Zambia. The study included quantitative and qualitative surveys with health care providers and women who recently delivered, as well as health facility observations and qualitative interviews with health facility supervisors. Our results show that clients who delivered at a facility where our intervention took place had a decreased likelihood of experiencing disrespect and abuse and an increased provision of pain management support. Our findings suggest that facility-based approaches informed by behavioral science have the potential to increase provision of respectful care and decrease the prevalence of mistreatment in low-resource settings. A large-scale evaluation of these interventions across settings could contribute valuable evidence around low-cost solutions to promote respectful maternity care.

Abstract Background Opioid-related overdose deaths have been increasing in the United States (U.S.) in the last twenty years, creating a public health challenge. Take-home naloxone is an effective strategy for preventing opioid-related overdose death, but its widespread use is particularly challenging in smaller cities, towns, and rural areas where it may be stigmatized and/or poorly understood. Methods We analyzed data on knowledge and beliefs about drug use and naloxone among the general public in Nebraska, a largely rural state in the Great Plains region of the U.S., drawing on the 2020 Nebraska Annual Social Indicators Survey. Results Respondents reported negative beliefs about people who use drugs (PWUD) and little knowledge of naloxone. Over half reported that members of their community view PWUD as blameworthy, untrustworthy, and dangerous. Approximately 31% reported being unaware of naloxone. Only 15% reported knowing where to obtain naloxone and less than a quarter reported knowing how to use it. Knowing where to obtain naloxone is associated with access to opioids and knowing someone who has recently overdosed, but having ever used opioids or being close to someone who uses opioids is not associated with naloxone knowledge. Finally, almost a quarter of respondents endorsed the belief that people who use opioids will use more if they have access to naloxone. Conclusion Our findings highlight stigmatizing beliefs about PWUD and underscore the need for further education on naloxone as an effective strategy to reduce opioid-related overdose death. We highlight the implications of these findings for public education efforts tailored to non-urban communities.

Category: Ankle; Basic Sciences/Biologics; Sports Introduction/Purpose: The treatment of progressive collapsing foot deformity (PCFD) typically begins with nonoperative management including physical therapy, bracing, nonsteroidal anti-inflammatory medications, and activity modifications. Surgical intervention is not typically performed until nonoperative treatment has failed. Corticosteroid injections into the posterior tibial tendon sheath (PTTS) is a burgeoning nonoperative treatment modality for PCFD. The purpose of our study was to assess the safety of ultrasound-guided corticosteroid injections into the posterior tibial tendon sheath for posterior tibialis tendon tendinopathy. Secondary outcomes include duration of pain relief, amount of pain relief, need for repeat injections and progression to surgery. Methods: We retrospectively reviewed all patients in our electronic medical record who underwent a PTTS steroid injection between 2015 to 2020 for the diagnosis of posterior tibial tendon dysfunction, and/or posterior tibialis tendon insufficiency, and/or ankle pain. Demographic information was obtained from the patient record in addition to MRI data, clinical response to injection based on follow up visits, number of total injections, and progression to surgery. Thirty-eight posterior tibial tendon sheath ultrasound-guided injections in 33 patients met criteria during the 5 year study period. Results: Thirty-three patients were included in the study with 38 injections. Two patients (6.1%) had 3 posterior tibial tendon injections, one patient (3%) had 2 injections, and the rest had only a single injection yielding a total of 38 injections included in the study. Eighteen of 38 (47%) injections yielded good or better pain relief. Seven of 33 patients (21%) progressed to surgery. There were no reported complications with the 38 performed injections. Conclusion: Ultrasound-guided corticosteroid injections into the posterior tibial tendon sheath is a safe nonoperative treatment modality for posterior tibialis tendon tendinopathy. The efficacy of the injection appears highly variable with 47% of injections yielding 'good' or better clinical results. When evaluating BMI, obese patients (BMI >= 30.0) were found to have a more sustained response to injection (P = 0.029) and more pain relief (P = 0.049) compared to non-obese patients.

Concerns about the mental health of students, trainees and staff at universities and medical schools have been growing for many years. Recently, these have been exacerbated by the COVID-19 pandemic and a period of heightened reckoning and protests about systemic racism in the United States in 2020. To better understand the mental health of medical students and biomedical doctoral students at the University of North Carolina at Chapel Hill during this challenging period, we performed a cross-sectional study (n=957) using institutional annual survey data on measures of depression, anxiety, hazardous alcohol use, problems related to substance use, and suicidal ideation. These data were collected in 2019 and 2020, and were analyzed by type of training program, race/ethnicity, gender, sexual orientation, and survey year. Results indicated significant differences for rates of depression, anxiety, and suicidal ideation, with biomedical doctoral students showing greater incidence than medical students, and historically excluded students (e.g., people of color, women, LGBQ+ trainees) showing greater incidence compared to their peers. Of note, mental health remained poor for biomedical doctoral students in 2020 and declined for those belonging to historically excluded populations. The high rates of depression, anxiety, and suicidal ideation reported suggest that training environments need to be improved and support for mental health increased.

Neutrophils are the most abundant white blood cell in the body and are key participants in the defense against fungal infections. Fungal infections occur often in patients with cirrhosis and are associated with increased 30‐day and 90‐day mortality. Previous studies have shown that specific neutrophil functions are abnormal in patients with cirrhosis, although the extent of neutrophil dysfunction is not well understood. We tested the ability of neutrophils from 21 hospitalized patients with cirrhosis and 23 healthy control patients to kill Candida albicans, a common fungal pathogen in patients with cirrhosis. Using an assay, we also measured the ability of neutrophils to coordinate multicellular, synchronized control of C. albicans hyphae through a process known as swarming. We found that neutrophils from patients with cirrhosis have significantly decreased fungicidal capacity compared with healthy control neutrophils (53% vs. 74%, P

Neutrophils employ several mechanisms to control the growth of fungi, including enzymes, reactive oxygen species, extracellular traps, and formation of “swarms”. Here, Hopke et al. study how the different mechanisms work together, using an in vitro assay with human neutrophils and clusters of live Candida cells.

Background: Family caregivers of older people with Alzheimer’s dementia (PWD) often need to advocate and resolve health-related conflicts (e.g., determining treatment necessity, billing errors, and home health extensions). As they deal with these health system conflicts, family caregivers experience unnecessary frustration, anxiety, and stress. The goal of this research was to apply a negotiation framework to resolve real-world family caregiver–older adult conflicts. Methods: We convened an interdisciplinary team of national community-based family caregivers, social workers, geriatricians, and negotiation experts (n = 9; Illinois, Florida, New York, and California) to examine the applicability of negotiation and conflict management frameworks to three older adult–caregiver conflicts (i.e., caregiver–older adult, caregiver–provider, and caregiver–caregiver). The panel of caregivers provided scenarios and dialogue describing conflicts they experienced in these three settings. A qualitative analysis was then performed grouping the responses into a framework matrix. Results: Upon presenting the three conflicts to the caregivers, 96 responses (caregiver–senior), 75 responses (caregiver–caregiver), and 80 responses (caregiver–provider) were generated. A thematic analysis showed that the statements and responses fit the interest–rights–power (IRP) negotiation framework. Discussion: The interests–rights–power (IRP) framework, used in business negotiations, provided insight into how caregivers experienced conflict with older adults, providers, and other caregivers. Future research is needed to examine applying the IRP framework in the training of caregivers of older people with Alzheimer’s dementia.

We introduce for the first time a new product line able to make high accuracy measurements of a number of water chemistry parameters in situ: i.e., submerged in the environment including in the deep sea (to 6,000 m). This product is based on the developments of in situ lab on chip technology at the National Oceanography Centre (NOC), and the University of Southampton and is produced under license by Clearwater Sensors Ltd., a start-up and industrial partner in bringing this technology to global availability and further developing its potential. The technology has already been deployed by the NOC, and with their partners worldwide over 200 times including to depths of ∼4,800 m, in turbid estuaries and rivers, and for up to a year in seasonally ice-covered regions of the arctic. The technology is capable of making accurate determinations of chemical and biological parameters that require reagents and which produce an electrical, absorbance, fluorescence, or luminescence signal. As such it is suitable for a wide range of environmental measurements. Whilst further parameters are in development across this partnership, Nitrate, Nitrite, Phosphate, Silicate, Iron, and pH sensors are currently available commercially. Theses sensors use microfluidics and optics combined in an optofluidic chip with electromechanical valves and pumps mounted upon it to mix water samples with reagents and measure the optical response. An overview of the sensors and the underlying components and technologies is given together with examples of deployments and integrations with observing platforms such as gliders, autonomous underwater vehicles and moorings.

Auditory nerve fibers (ANFs) innervating the same inner hair cell (IHC) may have identical frequency tuning but different sound response properties. In cat and guinea pig, ANF response properties correlate with afferent synapse morphology and position on the IHC, suggesting a causal structure-function relationship. In mice, this relationship has not been fully characterized. Here we measured the emergence of synaptic morphological heterogeneities during maturation of the C57BL/6J mouse cochlea by comparing postnatal day 17 (p17, ∼3 days after hearing onset) with p34, when the mouse cochlea is mature. Using serial block face scanning electron microscopy and three-dimensional reconstruction we measured the size, shape, vesicle content, and position of 70 ribbon synapses from the mid-cochlea. Several features matured over late postnatal development. From p17 to p34, presynaptic densities (PDs) and post-synaptic densities (PSDs) became smaller on average (PDs: 0.75 to 0.33; PSDs: 0.58 to 0.31 μm2) and less round as their short axes shortened predominantly on the modiolar side, from 770 to 360 nm. Membrane-associated synaptic vesicles decreased in number from 53 to 30 per synapse from p17 to p34. Anatomical coupling, measured as PSD to ribbon distance, tightened predominantly on the pillar side. Ribbons became less spherical as long-axes lengthened only on the modiolar side of the IHC, from 372 to 541 nm. A decreasing gradient of synaptic ribbon size along the modiolar-pillar axis was detected only at p34 after aligning synapses of adjacent IHCs to a common reference frame (median volumes in nm3 × 106: modiolar 4.87; pillar 2.38). The number of ribbon-associated synaptic vesicles scaled with ribbon size (range 67 to 346 per synapse at p34), thus acquiring a modiolar-pillar gradient at p34, but overall medians were similar at p17 (120) and p34 (127), like ribbon surface area (0.36 vs. 0.34 μm2). PD and PSD morphologies were tightly correlated to each other at individual synapses, more so at p34 than p17, but not to ribbon morphology. These observations suggest that PDs and PSDs mature according to different cues than ribbons, and that ribbon size may be more influenced by cues from the IHC than the surrounding tissue.

Abstract Background Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by early‐onset non‐progressive involuntary movements. Although NKX2‐1 mutations or deletions are the cause of BHC, some BHC families do not have pathogenic alterations in the NKX2‐1 gene, indicating that mutations of non‐coding regulatory elements of NKX2‐1 may also play a role. Methods and Results By using whole‐genome microarray analysis, we identified a 117 Kb founder deletion in three apparently unrelated BHC families that were negative for NKX2‐1 sequence variants. Targeted next generation sequencing analysis confirmed the deletion and showed that it was part of a complex local genomic rearrangement. In addition, we also detected a 648 Kb de novo deletion in an isolated BHC case. Both deletions are located downstream from NKX2‐1 on chromosome 14q13.2‐q13.3 and share a 33 Kb smallest region of overlap with six previously reported cases. This region has no gene but contains multiple evolutionarily highly conserved non‐coding sequences. Conclusion We propose that the deletion of potential regulatory elements necessary for NKX2‐1 expression in this critical region is responsible for BHC phenotype in these patients, and this is a novel disease‐causing mechanism for BHC.

Objective: The aim of this study was to present safety, health and well-being profiles of workers within five occupations: call center work (N = 139), corrections (N = 85), construction (N = 348), homecare (N = 149), and parks and recreation (N = 178).Methods: Baseline data from the Data Repository of Oregon's Healthy Workforce Center were used. Measures were compared with clinical healthcare guidelines and national norms.Results: The prevalence of health and safety risks for adults was as follows: overweight (83.2%), high blood pressure (16.4%), injury causing lost work (9.9%), and reported pain (47.0%). Young workers were least likely to report adequate sleep (46.6%). Construction workers reported the highest rate of smoking (20.7%). All of the adult workers reported significantly lower general health than the general population.Conclusion: The number of workers experiencing poor safety, health and well-being outcomes suggest the need for improved working conditions.

Patient and family communication is a well-known factor associated with improved patient outcomes. During the COVID-19 pandemic, visitation restrictions meant communication with patients and their families became a challenge, particularly with intubated patients in the intensive care unit. As the hospital filled with COVID-19 patients, medical students and physicians at Albany Medical Center identified the urgent need for a better communication method with families. In response, the COVID-19 Compassion Coalition (CCC) was formed. The CCC’s goal was to decrease the distress felt by families unable to visit their hospitalized loved ones. They developed a streamlined process for videoconferencing between patients on COVID-19 units and their families by using tablets. Having medical students take responsibility for this process allowed nurses and physicians to focus on patient care. Incorporating videoconferencing technology can allow physicians and nurses to better connect with families, especially during unprecedented times like a pandemic.

In the western U.S., long-term fire suppression has led to a buildup of surface and ladder fuels, increasing the severity of fires. Coupled with increased home building in the wildland urban interface and global climate change, much of the western U.S. is facing unprecedented risk of catastrophic wildland fires. Given the almost 30 million acres of forestland in California, and the impacts to human community health and safety and natural systems that stem from uncontrolled fires, it is imperative that we understand the underlying processes and conditions in the landscape that determine fire impacts. In October of 2017, Sonoma County, California experienced three significant fires that resulted in loss of life and property, as well as impacts to natural systems. Sonoma County Ag + Open Space—with support from a team of technical consultants and in partnership with NASA and other experts—researched the impacts of the fires to woody vegetation within areas that burned during wind-driven and non-wind driven events. Using high-resolution aerial imagery, we mapped canopy condition of woody vegetation and used machine learning techniques to determine the importance of landscape measures of vegetation structure, land cover type, topography, climate and weather, and nearness to streams as predictors of woody canopy condition for areas that burned during the October 2017 fires. Across the landscapes, riparian and mesic vegetation types exhibited the least canopy damage, followed by upland hardwood forest types. Shrub and upland conifer types exhibited the most canopy damage. Measures of vegetation structure derived from lidar data are the most important predictors of post-fire woody canopy condition, in addition to slope-aspect, proximate vegetation community types, and distance to streams. In general, the higher the density of shrubs and fire-adapted vegetation types, the higher the density of ladder fuels, and the greater the distance from streams, the higher the canopy damage. This study emphasizes the value of high resolution airborne lidar for mapping vegetation type and structure and building locations at a scale large enough to inform local management decisions. The study also documents pre- and post-fire baseline conditions to support the long-term evaluation of vegetation impacts and provides remote sensing and analysis tools to better plan for, manage, and mitigate future extreme wildfire through the lens of climate and extreme event resiliency, community safety and ecosystem health.

Abstract Background Dissemination of evidence-based practices that can reduce morbidity and mortality is important to combat the growing opioid overdose crisis in the USA. Research and expert consensus support reducing high-dose opioid therapy, avoiding risky opioid-benzodiazepine combination therapy, and promoting multi-modal, collaborative models of pain care. Collaborative care interventions that support primary care providers have been effective in medication tapering. We developed a patient-centered Primary Care-Integrated Pain Support (PIPS) collaborative care clinical program based on effective components of previous collaborative care interventions. Implementation facilitation, a multi-faceted and dynamic strategy involving the provision of interactive problem-solving and support during implementation of a new program, is used to support key organizational staff throughout PIPS implementation. The primary aim of this study is to evaluate the effectiveness of the implementation facilitation strategy for implementing and sustaining PIPS in the Veterans Health Administration (VHA). The secondary aim is to examine the effect of the program on key patient-level clinical outcomes—transitioning to safer regimens and enhancing access to complementary and integrative health treatments. The tertiary aim is to determine the categorical costs and ultimate budget impact of PIPS implementation. Methods This multi-site study employs an interrupted time series, hybrid type III design to evaluate the effectiveness of implementation facilitation for a collaborative care clinical program—PIPS—in primary care clinics in three geographically diverse VHA health care systems (sites). Participants include pharmacists and allied staff involved in the delivery of clinical pain management services as well as patients. Eligible patients are prescribed either an outpatient opioid prescription greater than or equal to 90 mg morphine equivalent daily dose or a combination opioid-benzodiazepine regimen. They must also have an upcoming appointment in primary care. The Consolidated Framework for Implementation Research will guide the mixed methods work across the formative evaluation phases and informs the selection of activities included in implementation facilitation. The RE-AIM framework will be used to assess Reach, Effectiveness, Adoption, Implementation, and Maintenance of PIPS. Discussion This implementation study will provide important insight into the effectiveness of implementation facilitation to enhance uptake of a collaborative care program in primary care, which targets unsafe opioid prescribing practices.

Abstract Background Childhood disintegrative disorder (CDD) is a rare form of autism spectrum disorder (ASD) of unknown etiology. It is characterized by late-onset regression leading to significant intellectual disability (ID) and severe autism. Although there are phenotypic differences between CDD and other forms of ASD, it is unclear if there are neurobiological differences. Methods We pursued a multidisciplinary study of CDD (n = 17) and three comparison groups: low-functioning ASD (n = 12), high-functioning ASD (n = 50), and typically developing (n = 26) individuals. We performed whole-exome sequencing (WES), copy number variant (CNV), and gene expression analyses of CDD and, on subsets of each cohort, non-sedated functional magnetic resonance imaging (fMRI) while viewing socioemotional (faces) and non-socioemotional (houses) stimuli and eye tracking while viewing emotional faces. Results We observed potential differences between CDD and other forms of ASD. WES and CNV analyses identified one or more rare de novo, homozygous, and/or hemizygous (mother-to-son transmission on chrX) variants for most probands that were not shared by unaffected sibling controls. There were no clearly deleterious variants or highly recurrent candidate genes. Candidate genes that were found to be most conserved at variant position and most intolerant of variation, such as TRRAP, ZNF236, and KIAA2018, play a role or may be involved in transcription. Using the human BrainSpan transcriptome dataset, CDD candidate genes were found to be more highly expressed in non-neocortical regions than neocortical regions. This expression profile was similar to that of an independent cohort of ASD probands with regression. The non-neocortical regions overlapped with those identified by fMRI as abnormally hyperactive in response to viewing faces, such as the thalamus, cerebellum, caudate, and hippocampus. Eye-tracking analysis showed that, among individuals with ASD, subjects with CDD focused on eyes the most when shown pictures of faces. Conclusions Given that cohort sizes were limited by the rarity of CDD, and the challenges of conducting non-sedated fMRI and eye tracking in subjects with ASD and significant ID, this is an exploratory study designed to investigate the neurobiological features of CDD. In addition to reporting the first multimodal analysis of CDD, a combination of fMRI and eye-tracking analyses are being presented for the first time for low-functioning individuals with ASD. Our results suggest differences between CDD and other forms of ASD on the neurobiological as well as clinical level.

Technological advances have created unprecedented opportunities for online financial education that can be used to improve financial literacy and money management practices. While online financial education programs have become popular, relevant research and theoretical frameworks have rarely been considered in the development of such programs. This article synthesizes lessons from literature and theories for the development of an effective online financial education program. Drawing from literature on financial literacy education and online education, implications and recommendations for integrating technology into online financial education programs for adults are discussed.

Advancing our understanding of ocean biogeochemistry, biology, and ecosystems relies on the ability to make observations both in the ocean and at the critical boundaries between the ocean and other earth systems at relevant spatial and temporal scales. After decades of advancement in ocean observing technologies, one of the key remaining challenges is how to cost-effectively make measurements at the increased resolution necessary for illuminating complex system processes and rapidly evolving changes. In recent years, biogeochemical in situ sensors have been emerging that are threefold or more lower in cost than established technologies; the cost reduction for many biological in situ sensors has also been significant, although the absolute costs are still relatively high. Cost savings in these advancements has been driven by miniaturization, new methods of packaging, and lower-cost mass-produced components such as electronics and materials. Recently, field projects have demonstrated the potential for science-quality data collection via large-scale deployments using cost-effective sensors and deployment strategies. In the coming decade, it is envisioned that ocean biogeochemistry and biology observations will be revolutionized by continued innovation in sensors with increasingly low price points and the scale-up of deployments of these in situ sensor technologies. The goal of this study is therefore to: (1) provide a review of existing sensor technologies that are already achieving cost-effectiveness compared with traditional instrumentation, (2) present case studies of cost-effective in situ deployments that can provide insight into methods for bridging observational gaps, (3) identify key challenge areas where progress in cost reduction is lagging, and (4) present a number of potentially transformative directions for future ocean biogeochemical and biological studies using cost-effective technologies and deployment strategies.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

In this study, we expand upon the biogeography of biological soil crusts (BSCs) and provide molecular insights into the microbial community and biochemical dynamics along the vertical BSC column structure, and across a transect of increasing BSC surface coverage in the central Mojave Desert, CA, United States. Next generation sequencing reveals a bacterial community profile that is distinct among BSCs in the southwestern United States. Distribution of major phyla in the BSC topsoils included Cyanobacteria (33 ± 8%), Proteobacteria (26 ± 6%), and Chloroflexi (12 ± 4%), with Phormidium being the numerically dominant genus. Furthermore, BSC subsurfaces contained Proteobacteria (23 ± 5%), Actinobacteria (20 ± 5%), and Chloroflexi (18 ± 3%), with an unidentified genus from Chloroflexi (AKIW781, order) being numerically dominant. Across the transect, changes in distribution at the phylum (p < 0.0439) and genus (p < 0.006) levels, including multiple biochemical and geochemical trends (p < 0.05), positively correlated with increasing BSC surface coverage. This included increases in (a) Chloroflexi abundance, (b) abundance and diversity of Cyanobacteria, (b) OTU-level diversity in the topsoil, (c) OTU-level differentiation between the topsoil and subsurface, (d) intracellular ATP abundances and catalase activities, and (e) enrichments in clay, silt, and varying elements, including S, Mn, Co, As, and Pb, in the BSC topsoils. In sum, these studies suggest that BSCs from regions of differing surface coverage represent early successional stages, which exhibit increasing bacterial diversity, metabolic activities, and capacity to restructure the soil. Further, these trends suggest that BSC successional maturation and colonization across the transect are inhibited by metals/metalloids such as B, Ca, Ti, Mn, Co, Ni, Mo, and Pb.

Quantitative relationship between the magnitude of variation in minor histocompatibility antigens (mHA) and graft versus host disease (GVHD) pathophysiology in stem cell transplant (SCT) donor-recipient pairs (DRP) is not established. In order to elucidate this relationship, whole exome sequencing (WES) was performed on 27 HLA matched related (MRD), & 50 unrelated donors (URD), to identify nonsynonymous single nucleotide polymorphisms (SNPs). An average 2,463 SNPs were identified in MRD, and 4,287 in URD DRP (p

Background: Mindfulness-based, in-person programs are effective at reducing stress and enhancing resilience in military and civilian samples, yet few studies have examined or compared training offered via real-time, interactive social media. Such a program would have a wider-reach and could include those unable to attend in-person. There is also interest in resolving ambiguity about the effects of mindfulness training on individual difference variables, such as self-compassion., Objective: The purpose of this research was to compare pre/post self-compassion for three interventions; Mindfulness-based Stress Reduction delivered in-person (IP), mindfulness meditation training delivered via a Virtual World (VW), and a wait-list Control Group (CG) among active duty and veteran U.S. military., Methods: A 2 (pre/post)×3 (group) factorial design was conducted with 250 active duty and veteran U.S. Military service members, with self-compassion measures as dependent variables., Results: Self Compassion improved 10% for the IP group and 14% for the VW group, while the CG group did not improve. Combined treatment groups yielded a 10.3% improvement in self-compassion compared with no change in the CG and with a group×time interaction effect (p < 0.01). Participants with lower initial self-compassion experienced greater benefits than those with higher baseline self-compassion (p < 0.01)., Conclusion: IP and VW Mindfulness Meditation training were equally effective in increasing self-compassion. Adding effective on-line mindfulness delivery will promote self-compassion among a more extensive audience, likely yielding improved coping, confidence, connectedness, cheerfulness, steadiness, and self-satisfaction, while lessening anxiety, fear-of-failure, and stress among participants.

Importance: Physical therapy and glucocorticoid injections are initial treatment options for knee osteoarthritis, but available data indicate that most patients receive one or the other, suggesting they may be competing interventions. The initial cost difference for treatment can be substantial, with physical therapy often being more expensive at the outset, and cost-effectiveness analysis can aid patients and clinicians in making decisions., Objective: To investigate the incremental cost-effectiveness between physical therapy and intra-articular glucocorticoid injection as initial treatment strategies for knee osteoarthritis., Design, Setting, and Participants: This economic evaluation is a secondary analysis of a randomized clinical trial performed from October 1, 2012, to May 4, 2017. Health economists were blinded to study outcomes and treatment allocation. A randomized sample of patients seen in primary care and physical therapy clinics with a radiographically confirmed diagnosis of knee osteoarthritis were evaluated from the clinical trial with 96.2% follow-up at 1 year., Interventions: Physical therapy or glucocorticoid injection., Main Outcomes and Measures: The main outcome was incremental cost-effectiveness between 2 alternative treatments. Acceptability curves of bootstrapped incremental cost-effectiveness ratios (ICERs) were used to identify the proportion of ICERs under the specific willingness-to-pay level ($50 000-$100 000). Health care system costs (total and knee related) and health-related quality-of-life based on quality-adjusted life-years (QALYs) were obtained., Results: A total of 156 participants (mean [SD] age, 56.1 [8.7] years; 81 [51.9%] male) were randomized 1:1 and followed up for 1 year. Mean (SD) 1-year knee-related medical costs were $2113 ($4224) in the glucocorticoid injection group and $2131 ($1015) in the physical therapy group. The mean difference in QALY significantly favored physical therapy at 1 year (0.076; 95% CI, 0.02-0.126; P = .003). Physical therapy was the more cost-effective intervention, with an ICER of $8103 for knee-related medical costs, with a 99.2% probability that results fall below the willingness-to-pay threshold of $100 000., Conclusions and Relevance: A course of physical therapy was cost-effective compared with a course of glucocorticoid injections for patients with knee osteoarthritis. These results suggest that, although the initial cost of delivering physical therapy may be higher than an initial course of glucocorticoid injections, 1-year total knee-related costs are equivalent, and greater improvement in QALYs may justify the initial higher costs., Trial Registration: ClinicalTrials.gov Identifier: NCT01427153.

Abstract: Spiering, BA, Walker, LA, Larcom, K, Frykman, PN, Allison, SC, and Sharp, MA. Predicting soldier task performance from physical fitness tests: reliability and construct validity of a soldier task test battery. J Strength Cond Res 35(10): 2749-2755, 2021-The purpose of this study was to determine the reliability and construct validity of a battery of tests designed to assess soldier task performance. In the first part of the study (designed to assess test-retest reliability), 33 enlisted soldiers (31 men, 2 women; 23 ± 3 years; 1.75 ± 0.08 m; and 81.4 ± 12.8 kg) completed a 4-event "soldier task test battery" (STTB) on 4 occasions, each separated by at least 1 week. The STTB consisted of the following tests, in order: (a) 30-m grenade throw for accuracy; (b) running long jump while wearing a 20.5-kg load; (c) 1 repetition maximum box lift; and (d) 3.2-km load carriage time trial while wearing a 33-kg load. In the second part of the study (designed to assess construct validity), 41 male soldiers (22 ± 3 years; 1.75 ± 0.08 m; and 81.4 ± 12.9 kg) completed the STTB and a series of physical fitness tests. The physical fitness tests included measurements of body composition, muscular strength, muscular power, muscular endurance, and cardiovascular endurance. Overall performance on the STTB (reflected by the sum of z-scores across individual tests) demonstrated an intraclass correlation coefficient of 0.95 and was correlated to lean mass, V˙o2peak, and measures of muscular strength and power. Lean body mass and standing long jump predicted performance on the STTB (R2 = 0.41). In conclusion, this STTB can reliably assess performance of soldiering tasks. The relationships between the STTB and physical fitness tests can be used to develop training programs to prepare soldiers to perform physically demanding tasks., (Copyright © 2019 National Strength and Conditioning Association.)

Background: Attrition rate in new army recruits is higher than in incumbent troops. In the current study, we identified the risk factors for attrition due to injuries and physical fitness failure in recruit training. A variety of predictive models were attempted., Methods: This retrospective cohort included 19,769 Army soldiers of the Australian Defence Force receiving recruit training during a period from 2006 to 2011. Among them, 7692 reserve soldiers received a 28-day training course, and the remaining 12,077 full-time soldiers received an 80-day training course. Retrieved data included anthropometric measures, course-specific variables, injury, and physical fitness failure. Multivariate regression was used to develop a variety of models to predict the rate of attrition due to injuries and physical fitness failure. The area under the receiver operating characteristic curve was used to compare the performance of the models., Results: In the overall analysis that included both the 28-day and 80-day courses, the incidence of injury of any type was 27.8%. The 80-day course had a higher rate of injury if calculated per course (34.3% vs. 17.6% in the 28-day course), but lower number of injuries per person-year (1.56 vs. 2.29). Fitness test failure rate was significantly higher in the 28-day course (30.0% vs. 12.1%). The overall attrition rate was 5.2 and 5.0% in the 28-day and 80-day courses, respectively. Stress fracture was common in the 80-day course (n = 44) and rare in the 28-day course (n = 1). The areas under the receiver operating characteristic curves for the course-specific predictive models were relatively low (ranging from 0.51 to 0.69), consistent with "failed" to "poor" predictive accuracy. The course-combined models performed somewhat better than the course-specific models, with two models having AUC of 0.70 and 0.78, which are considered "fair" predictive accuracy., Conclusion: Attrition rate was similar between 28-day and 80-day courses. In comparison to the 80-day full course, the 28-day course had a lower rate of injury but a higher number of injuries per person-year and of fitness test failure. These findings suggest fitness level at the commencement of training is a critically important factor to consider when designing the course curriculum, particularly short courses.

Background: Both physical therapy and intraarticular injections of glucocorticoids have been shown to confer clinical benefit with respect to osteoarthritis of the knee. Whether the short-term and long-term effectiveness for relieving pain and improving physical function differ between these two therapies is uncertain., Methods: We conducted a randomized trial to compare physical therapy with glucocorticoid injection in the primary care setting in the U.S. Military Health System. Patients with osteoarthritis in one or both knees were randomly assigned in a 1:1 ratio to receive a glucocorticoid injection or to undergo physical therapy. The primary outcome was the total score on the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 1 year (scores range from 0 to 240, with higher scores indicating worse pain, function, and stiffness). The secondary outcomes were the time needed to complete the Alternate Step Test, the time needed to complete the Timed Up and Go test, and the score on the Global Rating of Change scale, all assessed at 1 year., Results: We enrolled 156 patients with a mean age of 56 years; 78 patients were assigned to each group. Baseline characteristics, including severity of pain and level of disability, were similar in the two groups. The mean (±SD) baseline WOMAC scores were 108.8±47.1 in the glucocorticoid injection group and 107.1±42.4 in the physical therapy group. At 1 year, the mean scores were 55.8±53.8 and 37.0±30.7, respectively (mean between-group difference, 18.8 points; 95% confidence interval, 5.0 to 32.6), a finding favoring physical therapy. Changes in secondary outcomes were in the same direction as those of the primary outcome. One patient fainted while receiving a glucocorticoid injection., Conclusions: Patients with osteoarthritis of the knee who underwent physical therapy had less pain and functional disability at 1 year than patients who received an intraarticular glucocorticoid injection. (ClinicalTrials.gov number, NCT01427153.)., (Copyright © 2020 Massachusetts Medical Society.)

Introduction: Corticosteroid injections (CSIs) are commonly used as an initial or a primary intervention for knee osteoarthritis (OA). Consistent evidence indicates CSIs offer symptom relief with conflicting reports regarding long-term efficacy. Physical therapy (PT) offers a non-invasive alternative. There is moderate evidence suggesting short-term and long-term symptom relief and functional improvement with PT interventions. Patients with knee OA are more commonly prescribed CSI than PT prior to total joint replacement. UnitedHealthcare and Military Health System data show substantially more total knee replacement patients receive preoperative CSI than PT. There are no studies comparing CSI to a PT approach in individuals with knee OA. The primary objective of this study is to compare the effectiveness of CSI to PT in individuals with knee OA at 1, 2 and 12 months., Methods and Analysis: We plan to recruit 156 participants meeting established knee OA criteria. Following informed consent, participants will be randomised to receive either CSI or PT. All participants will receive instruction on recommended exercise and weight control strategies plus usual medical care. The CSI intervention consisting of 3 injections and the PT intervention consisting of 8-12 sessions will be spaced over 12 months. Measures of the dependent variables (DVs) will occur at baseline, 4 weeks, 8 weeks, 6 months and 12 months post enrolment. This pragmatic, randomised clinical trial will be a mixed-model 2×5 factorial design. The independent variables are treatment (CSI and PT) and time with five levels from baseline to 1 year. The primary DV is the Western Ontario & McMaster Universities Arthritis Index (WOMAC). We will also compare healthcare utilisation between the 2 groups., Ethics and Dissemination: The protocol was approved by the Madigan Army Medical Center Institutional Review Board. The authors intend to publish the results in a peer-reviewed source., Trial Registration Number: NCT01427153., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Early detection and treatment of high-grade dysplasia (HGD) in Barrett's esophagus may reduce the risk of developing esophageal adenocarcinoma. Confocal endomicroscopy (CLE) has shown advantages over routine white-light endoscopic surveillance with biopsy for histological examination; however, CLE is compromised by insufficient contrast and by intra- and interobserver variation. An FDA-approved PDT photosensitizer was used here to reveal morphological and textural features similar to those found in histological analysis. Support vector machines were trained using the aforementioned features to obtain an automatic and robust detection of HGD. Our results showed 95% sensitivity and 87% specificity using the optimal feature combination and demonstrated the potential for extension to a three-dimensional cell model.

High-grade dysplasia (HGD) in Barrett’s esophagus (BE) poses increased risk for developing esophageal adenocarcinoma. To date, early detection and treatment of HGD regions are still challenging due to the sampling error from tissue biopsy and relocation error during the treatment after histopathological analysis. In this study, CP-A (metaplasia) and CP-B (HGD) cell lines were used to investigate the “seek-and-treat” potential using 5-aminolevulinic acid-induced protoporphyrin IX (PpIX). The photodynamic therapy photosensitizer then provides both a phototoxic effect and additional image contrast for automatic detection and real-time laser treatment. Complementary to our studies on automatic classification, this work focused on characterizing subcellular irradiation and the potential phototoxicity on both metaplasia and HGD. The treatment results showed that the HGD cells are less viable than metaplastic cells due to more PpIX production at earlier times. Also, due to mitochondrial localization of PpIX, a better killing effect was achieved by involving mitochondria or whole cells compared with just nucleus irradiation in the detected region. With the additional toxicity given by PpIX and potential morphological/textural differences for pattern recognition, this cellular platform serves as a platform to further investigate real-time “seek-and-treat” strategies in three-dimensional models for improving early detection and treatment of BE., (© 2015 Society of Photo-Optical Instrumentation Engineers (SPIE))