The Importance of Th2 Immune Responses in Mediating the Progression of Gastritis-Associated Metaplasia to Gastric Cancer.

Gastric cancer is one of the leading causes of cancer deaths worldwide, with chronic gastritis representing the main predisposing factor initiating the cascade of events leading to metaplasia and eventually progressing to cancer. A widely accepted classification distinguishes between autoimmune and environmental atrophic gastritis, mediated, respectively, by T cells promoting the destruction of the oxyntic mucosa, and chronic H. pylori infection, which has also been identified as the major risk factor for gastric cancer. The original dogma posits Th1 immunity as a main causal factor for developing gastritis and metaplasia. Recently, however, it has become evident that Th2 immune responses play a major role in the events causing chronic inflammation leading to tumorigenesis, and in this context, many different cell types and cytokines are involved. In particular, the activity of cytokines, such as IL-33 and IL-13, and cell types, such as mast cells, M2 macrophages and eosinophils, are intertwined in the process, promoting chronic gastritis-dependent and more diffuse metaplasia. Herein, we provide an overview of the critical events driving the pathology of this disease, focusing on the most recent findings regarding the importance of Th2 immunity in gastritis and gastric metaplasia.

Small Steps over time: A longitudinal usability test of an automated interactive text messaging intervention to support self-management of depression and anxiety symptoms.

BACKGROUND: Digital mental health interventions (DMHIs) offer potential solutions for addressing mental health care gaps, but often suffer from low engagement. Text messaging is one promising medium for increasing access and sustaining user engagement with DMHIs. This paper examines the Small Steps SMS program, an 8-week, automated, adaptive text message-based intervention for depression and anxiety. METHODS: We conducted an 8-week longitudinal usability test of the Small Steps SMS program, recruiting 20 participants who met criteria for major depressive disorder and/or generalized anxiety disorder. Participants used the automated intervention for 8 weeks and completed symptom severity and usability self-report surveys after 4 and 8 weeks of intervention use. Participants also completed individual interviews to provide feedback on the intervention. RESULTS: Participants responded to automated messages on 70 % of study days and with 85 % of participants sending responses to messages in the 8th week of use. Usability surpassed established cutoffs for software that is considered acceptable. Depression symptom severity decreased significantly over the usability test, but reductions in anxiety symptoms were not significant. Participants noted key areas for improvement including addressing message volume, aligning message scheduling to individuals' availability, and increasing the customizability of content. LIMITATIONS: This study does not contain a control group. CONCLUSIONS: An 8-week automated interactive text messaging intervention, Small Steps SMS, demonstrates promise with regard to being a feasible, usable, and engaging method to deliver daily mental health support to individuals with symptoms of anxiety and depression.

A text messaging intervention to support the mental health of young adults: User engagement and feedback from a field trial of an intervention prototype.

Background: Young adults have high rates of mental health conditions, but most do not want or cannot access treatment. By leveraging a medium that young adults routinely use, text messaging programs have potential to keep young adults engaged with content supporting self-management of mental health issues and can be delivered inexpensively at scale. We designed an intervention that imparts strategies for self-managing mental health symptoms through interactive text messaging dialogues and engages users through novelty and variety in strategies (from cognitive behavioral therapy, acceptance and commitment therapy, and positive psychology) and styles of interaction (e.g., prompts, peer stories, writing tasks). Methods: The aim of this mixed-methods study was to pilot 1- and 2-week versions of an interactive text messaging intervention among young adults (ages 18-25), and to obtain feedback to guide intervention refinements. Young adults were recruited via a mental health advocacy website and snowball sampling at a North American University. We used Wizard-of-Oz methods in which study staff sent messages based on a detailed script. Transcripts of interviews were subject to qualitative analysis to identify aspects of the program that need improvements, and to gather participant perspectives on possible solutions. Results: Forty-eight individuals ages 18-25 participated in the study (mean age: 22.0). 85 % responded to the program at least once. Among those who ever responded, they replied to messages on 85 % of days, and with engagement sustained over the study period. Participants endorsed the convenience of text messaging, the types of interactive dialogues, and the variety of content. They also identified needed improvements to message volume, scheduling, and content. Conclusions: Young adults showed high levels of engagement and satisfaction with a texting program supporting mental health self-management. The program may be improved through refining personalization, timing, and message volume, and extending content to support use over a longer timeframe. If shown to be effective in randomized trials, this program has potential to help address a substantial treatment gap in young adults' mental health.

System design of a text messaging program to support the mental health needs of non-treatment seeking young adults.

Young adults (ages 18-25) experience the highest levels of mental health problems of any adult age group, but have the lowest mental health treatment rates. Text messages are the most used feature on the mobile phone and provide an opportunity to reach non-treatment engaged users throughout the day in a conversational manner. We present the design of an automated text message-based intervention for symptom self-management. The intervention comprises: (1) psychological strategies (i.e., types of evidence-based techniques leveraged to achieve symptom reduction) and (2) interaction types or the form that intervention content takes as it is delivered to and elicited from users.

Meeting Users Where They Are: User-centered Design of an Automated Text Messaging Tool to Support the Mental Health of Young Adults.

Young adults have high rates of mental health conditions, but most do not want or cannot access formal treatment. We therefore recruited young adults with depression or anxiety symptoms to co-design a digital tool for self-managing their mental health concerns. Through study activities-consisting of an online discussion group and a series of design workshops-participants highlighted the importance of easy-to-use digital tools that allow them to exercise independence in their self-management. They described ways that an automated messaging tool might benefit them by: facilitating experimentation with diverse concepts and experiences; allowing variable depth of engagement based on preferences, availability, and mood; and collecting feedback to personalize the tool. While participants wanted to feel supported by an automated tool, they cautioned against incorporating an overtly human-like motivational tone. We discuss ways to apply these findings to improve the design and dissemination of digital mental health tools for young adults.

Involving Crowdworkers with Lived Experience in Content-Development for Push-Based Digital Mental Health Tools: Lessons Learned from Crowdsourcing Mental Health Messages.

Digital tools can support individuals managing mental health concerns, but delivering sufficiently engaging content is challenging. This paper seeks to clarify how individuals with mental health concerns can contribute content to improve push-based mental health messaging tools. We recruited crowdworkers with mental health symptoms to evaluate and revise expert-composed content for an automated messaging tool, and to generate new topics and messages. A second wave of crowdworkers evaluated expert and crowdsourced content. Crowdworkers generated topics for messages that had not been prioritized by experts, including self-care, positive thinking, inspiration, relaxation, and reassurance. Peer evaluators rated messages written by experts and peers similarly. Our findings also suggest the importance of personalization, particularly when content adaptation occurs over time as users interact with example messages. These findings demonstrate the potential of crowdsourcing for generating diverse and engaging content for push-based tools, and suggest the need to support users in meaningful content customization.

Differential response to targeted acupuncture by gender in patients with gastrointestinal cancer cachexia: secondary analysis of a randomized controlled trial.

BACKGROUND: Cancer cachexia (CC) is a significant contributor to mortality and morbidity in patients with gastrointestinal (GI) cancer. Treatment options to prevent or halt the progression of CC are limited. Targeted acupuncture (TA) was used in GI patients with CC to evaluate for a potential gender effect. PATIENTS AND METHODS: Participants (n = 30) were recruited from two outpatient clinics in the northern central part of Florida. All participants were diagnosed with CC and GI cancers. A randomized, single-blind, placebo-controlled clinical trial was used to compare TA to non-targeted acupuncture (NTA) over the course of 8 weeks. Primary endpoints were weight and body composition changes measured by bioelectrical impedance analysis (BIA) and biomarker analysis (tumor necrosis factor (TNF)-α and leptin). Herein, gender differences across and within TA and NTA groups were examined as a secondary analysis. RESULTS: A significant (p = 0.026) interaction between weight and gender was noted, which manifested in a non-significant increase in the male intervention (MI) group, while TNF-α levels significantly increased by gender (p = 0.028) and group (p = 0.006) over the course of the study. All other groups either lost or did not change weight. The extracellular-to-intracellular water (ECW/ICW) ratio was significantly elevated for the TA group (p = 0.02) and for males (p = 0.009) at completion of the study. TNF-α and leptin levels were positively correlated within the MI group at the end of the study. CONCLUSION: A decrease in leptin in the MI group corresponded to higher appetite and weight gain. The elevated ECW/ICW ratio indicates an inflammatory response in the MI group. This gender-specific response may be based on hormone-specific regulation of food intake. Further studies with larger sample sizes are required to support the results.

Augmentation of Cancer Cachexia Components With Targeted Acupuncture in Patients With Gastrointestinal Cancers: A Randomized Controlled Pilot Study.

INTRODUCTION: Patients with gastrointestinal (GI) cancer-associated cachexia are at risk of high morbidity and mortality. This randomized single-blind pilot study compared the complementary use of targeted acupuncture (TA) with nontargeted acupuncture (NTA) for halting cachexia symptoms. METHODS: GI cancer patients with cachexia undergoing chemotherapy were assigned to receive 8 weekly sessions of either TA (n = 15) or NTA (n = 15) following a specific acupuncture protocol. Bioelectrical impedance analysis and weight were measured weekly. Biological markers, including C-reactive protein, prealbumin, tumor necrosis factor-α, lactate dehydrogenase (LDH), leptin, and ghrelin blood levels were determined at specific intervals. RESULTS: Prealbumin levels and fat-free mass were significantly higher in the NTA group at the end of the study, but remained stable in TA group. TA group had significantly lower (230 IU/L vs 288 IU/L, P = .04) LDH at the end of the study, but elevated tumor necrosis factor-α levels (13.15 pg/mL vs 9.24 pg/mL, P = .04). The absolute blood leptin and ghrelin levels decreased in the TA but remained stable in the NTA group. Both groups maintained weight, but the TA group trended toward weight gain during the last 2 weeks of the study. No adverse events related to acupuncture were reported. CONCLUSIONS: TA using predetermined, reproducible points may provide benefits to some patients with GI cancer cachexia by normalizing metabolic dysregulation. Elevated ghrelin levels are indicative of insulin resistance, which can lead to increased muscle loss represented by increased LDH activity in the NTA group. The pilot study provided completion rate and effect size for the primary outcome measures for a larger study. A longer treatment duration may be required to further refine these findings.

Explanation recruits comparison in a category-learning task.

Generating explanations can be highly effective in promoting category learning; however, the underlying mechanisms are not fully understood. We propose that engaging in explanation can recruit comparison processes, and that this in turn contributes to the effectiveness of explanation in supporting category learning. Three experiments evaluated the interplay between explanation and various comparison strategies in learning artificial categories. In Experiment 1, as expected, prompting participants to explain items' category membership led to (a) higher ratings of self-reported comparison processing and (b) increased likelihood of discovering a rule underlying category membership. Indeed, prompts to explain led to more self-reported comparison than did direct prompts to compare pairs of items. Experiment 2 showed that prompts to compare all members of a particular category ("group comparison") were more effective in supporting rule learning than were pairwise comparison prompts. Experiment 3 found that group comparison (as assessed by self-report) partially mediated the relationship between explanation and category learning. These results suggest that one way in which explanation benefits category learning is by inviting comparisons in the service of identifying broad patterns.

Body composition changes differ by gender in stomach, colorectal, and biliary cancer patients with cachexia: Results from a pilot study.

Few studies have examined the possibility that cachexia may affect men and women differently. This pilot study assessed gender differences in body composition in stomach, colorectal, and biliary cancer patients with cachexia. A sample of 38 participants (Female: Male = 17:21, mean age 57.4 years) were included if they were undergoing chemotherapy and experienced weight loss of 5% or more over a 6-month period. Bioelectrical impedance analysis (BIA) was applied to measure body composition. Phase angle (PA) and levels of extra-/intracellular water (ECW; ICW) were determined. Data were analyzed first by gender and then compared to age- and gender-matched healthy controls from the NHANES-III dataset. PA was lower (P < .01) in both genders compared with healthy controls, and PA was lower in female patients compared with male patients (P = .03). Male cancer patients with lower PA also had lower ICW levels compared with healthy controls (r = .98, P < .01). For female patients, PA and ICW were negatively correlated (r = .897, P < .01). A lower ECW/ICW ratio was highly correlated (r = .969 for men, r = .639 for women) with increased PA in cancer patients. ICW changes are gender-specific in patients with GI cancer. ECW/ICW ratios and PA may be suitable surrogate markers for gender-specific changes in cell composition and health status.

Explaining Constrains Causal Learning in Childhood.

Three experiments investigate how self-generated explanation influences children's causal learning. Five-year-olds (N = 114) observed data consistent with two hypotheses and were prompted to explain or to report each observation. In Study 1, when making novel generalizations, explainers were more likely to favor the hypothesis that accounted for more observations. In Study 2, explainers favored a hypothesis that was consistent with prior knowledge. Study 3 pitted a hypothesis that accounted for more observations against a hypothesis consistent with prior knowledge. Explainers were more likely to base generalizations on prior knowledge. Findings suggest that attempts to explain drive children to evaluate hypotheses using features of "good" explanations, or those supporting generalizations with broad scope, as informed by children's prior knowledge and observations.

Andean microrefugia: testing the Holocene to predict the Anthropocene.

Microrefugia are important for supporting populations during periods of unfavourable climate change and in facilitating rapid migration as conditions ameliorate. With ongoing anthropogenic climate change, microrefugia could have an important conservation value; however, a simple tool has not been developed and tested to predict which settings are microrefugial. We provide a tool based on terrain ruggedness modelling of individual catchments to predict Andean microrefugia. We tested the predictions using nine Holocene Polylepis pollen records. We used the mid-Holocene dry event, a period of peak aridity for the last 100 000 yr, as an analogue climate scenario for the near future. The results suggest that sites with high terrain rugosity have the greatest chance of sustaining mesic conditions under drier-than-modern climates. Fire is a feature of all catchments; however, an increase in fire is only recorded in settings with low rugosity. Owing to rising temperatures and greater precipitation variability, Andean ecosystems are threatened by increasing moisture stress. Our results suggest that high terrain rugosity helps to create more resilient catchments by trapping moisture through orographic rainfall and providing firebreaks that shelter forest from fire. On this basis, conservation policy should target protection and management of catchments with high terrain rugosity.

Learning cognitive behavior therapy.

BACKGROUND AND OBJECTIVES: Progress toward establishing treatments for mental disorders has been good, particularly for cognitive behavior therapy (CBT). However, there is considerable room for improvement. The goal of this study was to begin the process of investigating the potential for improving treatment outcome via improving our understanding of learning processes. METHODS: Individuals diagnosed with major depressive disorder (N = 20) participated in three computer-delivered CBT lessons for depression. Indices of learning were taken after each lesson, during three phone calls over the week following the lesson, and one week later. These were: (a) whether the participant thought about the lesson, (b) whether the participant applied the lesson, and (c) whether the participant generalized the lesson. Based on a predetermined list of therapy points (i.e., distinct ideas and principles), all participant responses were coded for the number of therapy points they thought about, applied, or generalized following each lesson. RESULTS: Less than half of the thoughts and applications were accurate. Generalization, but not thoughts nor application, was associated with improved depression scores one week later. LIMITATIONS: The follow up period was only one week later and there was no comparison group so we cannot speak to the long term outcome of these measures or generalize to other mental disorders. CONCLUSIONS: These results point to the importance of improving transfer of learning in CBT and represent a promising first step toward the development of methods to study and optimize learning of CBT so as to improve patient outcomes.

Novel intervention with acupuncture for anorexia and cachexia in patients with gastrointestinal tract cancers: a feasibility study.

PURPOSE/OBJECTIVES: To investigate the feasibility of using acupuncture as a complementary intervention to existing treatments and to evaluate the efficacy of acupuncture in improving appetite and slowing weight loss with patients with gastrointestinal (GI) tract cancers. 
 DESIGN: One-group pre- and postintervention feasibility study. 
 SETTING: Outpatient clinic for patients with cancer and a community setting, both in Florida. 
 SAMPLE: A convenience sample of seven adults with GI cancer.
 METHODS: Eight acupuncture sessions were provided during eight weeks. Data were collected using the visual analog scale (VAS) for appetite, Simplified Nutritional Appetite Questionnaire (SNAQ), Karnofsky Performance Status, and bioelectrical impedance analysis. 
 MAIN RESEARCH VARIABLES: Appetite, weight, attrition rate.
 FINDINGS: Seven patients with a mean age of 61 years completed the intervention. Acupuncture was well accepted, feasible, and safe without any reported side effects. Appetite showed improvement, with an average score of 3.04 on the VAS and 4.14 on SNAQ compared to the preintervention scores. The average weight loss was 1.32% compared to the baseline during an eight-week period. 
 CONCLUSIONS: The acupuncture intervention was feasible and indicated positive outcomes. Because of the small sample size and lack of a control group, statistical significance of effectiveness was not determined. Acupuncture seemed to improve appetite and slow weight loss in patients with GI cancers, so additional studies with a larger sample size and a variety of cancers are warranted. 
 IMPLICATIONS FOR NURSING: Oncology nurses are uniquely able to equip patients with information about complementary therapy modalities, such as acupuncture, which is a promising way to improve appetite and slow weight loss in patients with GI cancers.


A rational model of function learning.

Theories of how people learn relationships between continuous variables have tended to focus on two possibilities: one, that people are estimating explicit functions, or two that they are performing associative learning supported by similarity. We provide a rational analysis of function learning, drawing on work on regression in machine learning and statistics. Using the equivalence of Bayesian linear regression and Gaussian processes, which provide a probabilistic basis for similarity-based function learning, we show that learning explicit rules and using similarity can be seen as two views of one solution to this problem. We use this insight to define a rational model of human function learning that combines the strengths of both approaches and accounts for a wide variety of experimental results.

Influence of acupuncture on bioelectrical impedance measures in patients with gastrointestinal cancer: results of a pilot study.

BACKGROUND: Patients with gastrointestinal cancers often suffer from malnutrition and cachexia caused by inflammatory processes due to malignancy and therapeutic intervention. Evaluation of nutritional status and well-being of patients is essential to prevent or slow down the progression of cachexia. In addition, acupuncture as a complementary intervention may help reduce cachexia and unintentional weight loss. METHODS: Seven patients with cancers of the gastrointestinal tract enrolled in this pilot study were provided with eight acupuncture sessions in addition to their regular treatment schedule. Bioelectrical impedance analysis (BIA) measurements were taken at every other acupuncture session to evaluate the body composition of patients. BIA is a fast, inexpensive and non-invasive method for evaluating fluid, fat and muscle mass distribution which correlates with nutritional status. RESULTS: All patients enrolled in the pilot study completed the acupuncture intervention and BIA measurements. The average weight loss and reduction in body weight was 1.3%, which is less than the average weight loss of 5% reported in the literature. Both phase angle and fat-free mass decreased in patients, indicating a worsening of the condition. However, a shift from intracellular to extracellular fluid was not observed, which is usually associated with a loss of cell integrity. CONCLUSIONS: This pilot study indicates that patients tolerate acupuncture treatments well. The BIA results should be interpreted with caution due to the small sample size. A larger randomised placebo-controlled study is currently being conducted to further investigate the influence of acupuncture and to provide insights into BIA as a reliable tool for evaluating body composition in patients with gastrointestinal cancers.

Why are people bad at detecting randomness? A statistical argument.

Errors in detecting randomness are often explained in terms of biases and misconceptions. We propose and provide evidence for an account that characterizes the contribution of the inherent statistical difficulty of the task. Our account is based on a Bayesian statistical analysis, focusing on the fact that a random process is a special case of systematic processes, meaning that the hypothesis of randomness is nested within the hypothesis of systematicity. This analysis shows that randomly generated outcomes are still reasonably likely to have come from a systematic process and are thus only weakly diagnostic of a random process. We tested this account through 3 experiments. Experiments 1 and 2 showed that the low accuracy in judging whether a sequence of coin flips is random (or biased toward heads or tails) is due to the weak evidence provided by random sequences. While randomness judgments were less accurate than judgments involving non-nested hypotheses in the same task domain, this difference disappeared once the strength of the available evidence was equated. Experiment 3 extended this finding to assessing whether a sequence was random or exhibited sequential dependence, showing that the distribution of statistical evidence has an effect that complements known misconceptions.

Changes in global nitrogen cycling during the Holocene epoch.

Human activities have doubled the pre-industrial supply of reactive nitrogen on Earth, and future rates of increase are expected to accelerate. Yet little is known about the capacity of the biosphere to buffer increased nitrogen influx. Past changes in global ecosystems following deglaciation at the end of the Pleistocene epoch provide an opportunity to understand better how nitrogen cycling in the terrestrial biosphere responded to changes in carbon cycling. We analysed published records of stable nitrogen isotopic values (δ(15)N) in sediments from 86 lakes on six continents. Here we show that the value of sedimentary δ(15)N declined from 15,000 years before present to 7,056 ± 597 years before present, a period of increasing atmospheric carbon dioxide concentrations and terrestrial carbon accumulation. Comparison of the nitrogen isotope record with concomitant carbon accumulation on land and nitrous oxide in the atmosphere suggests millennia of declining nitrogen availability in terrestrial ecosystems during the Pleistocene-Holocene transition around 11,000 years before present. In contrast, we do not observe a consistent change in global sedimentary δ(15)N values during the past 500 years, despite the potential effects of changing temperature and nitrogen influx from anthropogenic sources. We propose that the lack of a single response may indicate that modern increases in atmospheric carbon dioxide and net carbon sequestration in the biosphere have the potential to offset recent increased supplies of reactive nitrogen in some ecosystems.

Explanation and prior knowledge interact to guide learning.

How do explaining and prior knowledge contribute to learning? Four experiments explored the relationship between explanation and prior knowledge in category learning. The experiments independently manipulated whether participants were prompted to explain the category membership of study observations and whether category labels were informative in allowing participants to relate prior knowledge to patterns underlying category membership. The experiments revealed a superadditive interaction between explanation and informative labels, with explainers who received informative labels most likely to discover (Experiments 1 and 2) and generalize (Experiments 3 and 4) a pattern consistent with prior knowledge. However, explainers were no more likely than controls to discover multiple patterns (Experiments 1 and 2), indicating that effects of explanation are relatively targeted. We suggest that explanation recruits prior knowledge to assess whether candidate patterns are likely to have broad scope (i.e., to generalize within and beyond study observations). This interpretation is supported by the finding that effects of explanation on prior knowledge were attenuated when learners believed prior knowledge was irrelevant to generalizing category membership (Experiment 4). This research provides evidence that explanation can serve as a mechanism for deploying prior knowledge to assess the scope of observed patterns.

The electrical conductivity of in vivo human uterine fibroids.

The purpose of this study was to determine the value of electrical conductivity that can be used for numerical modelling in vivo radiofrequency ablation (RFA) treatments of human uterine fibroids. No experimental electrical conductivity data have previously been reported for human uterine fibroids. In this study electrical data (voltage) from selected in vivo clinical procedures on human uterine fibroids were used to numerically model the treatments. Measured versus calculated power dissipation profiles were compared to determine uterine fibroid electrical conductivity. Numerical simulations were conducted utilising a wide range of values for tissue thermal conductivity, heat capacity and blood perfusion coefficient. The simulations demonstrated that power dissipation was insensitive to the exact values of these parameters for the simulated geometry, treatment duration, and power level. Consequently, it was possible to determine tissue electrical conductivity without precise knowledge of the values for these parameters. Results of this study showed that an electrical conductivity for uterine fibroids of 0.305 S/m at 37°C and a temperature coefficient of 0.2%/°C can be used for modelling Radio Frequency Ablation of human uterine fibroids at a frequency of 460 kHz for temperatures from 37°C to 100°C.