A structural characterization of shortcut features for prediction.

With the rising use of machine learning for healthcare applications, practitioners are increasingly confronted with the limitations of prediction models that are trained in one setting but meant to be deployed in several others. One recently identified limitation is so-called shortcut learning, whereby a model learns to associate features with the prediction target that do not maintain their relationship across settings. Famously, the watermark on chest x-rays has been demonstrated to be an instance of a shortcut feature. In this viewpoint, we attempt to give a structural characterization of shortcut features in terms of causal DAGs. This is the first attempt at defining shortcut features in terms of their causal relationship with a model's prediction target.

Catecholaminergic Polymorphic Ventricular Tachycardia: The Cardiac Arrest Where Epinephrine Is Contraindicated.

OBJECTIVES: To raise awareness among pediatric intensive care specialists of catecholaminergic polymorphic ventricular tachycardia; an uncommon cause of polymorphic ventricular tachycardia and ventricular fibrillation arrest in children and young adults where epinephrine (adrenaline), even when given according to international protocols, can be counter-productive and life-threatening. We review three cases of cardiac arrest in children, later proven to be catecholaminergic polymorphic ventricular tachycardia related, where delay in recognition of this condition resulted in significantly longer resuscitation efforts, more interventions, and a longer time to return of spontaneous circulation. DESIGN: Retrospective case series. SETTING: Tertiary children's hospital. PATIENTS AND RESULTS: Three previously well children 4, 5, and 10 years old presented with cardiac arrest triggered by light activity, partial water immersion, and running, respectively. Initial resuscitation was bystander cardiopulmonary resuscitation and community defibrillation in all three cases. Electrocardiograms revealed multifocal ventricular ectopy, and in two (4 and 10 yr old), this correlated with repeated administration of epinephrine during repeated ventricular tachycardia and ventricular fibrillation cardiac arrest resuscitation cycles. This ultimately resolved immediately (at 78 and 140 min, respectively) with IV opiates once catecholaminergic polymorphic ventricular tachycardia was suspected. During recovery, on extracorporeal membrane oxygenation, epinephrine challenge in two children induced polymorphic ventricular tachycardia, bidirectional ventricular tachycardia, and ventricular fibrillation, which was cardioverted with flecainide in the 4-year-old. The third case was recognized early as catecholaminergic polymorphic ventricular tachycardia and was managed by avoiding epinephrine and using opiates and general anesthesia after the initial (single) cardioversion, and had a much better clinical course, without recourse to extracorporeal membrane oxygenation. All three carried de novo RyR2 (cardiac ryanodine) mutations. CONCLUSIONS: Those involved in resuscitation of young people should be aware of catecholaminergic polymorphic ventricular tachycardia and be suspicious of persistent ventricular ectopy, polymorphic, or bidirectional ventricular tachycardia during resuscitation. Appropriate management is avoidance of epinephrine, administration of general anesthesia, IV opiates, and consideration of flecainide.

Predicting Larval Stage Distribution of Lobesia botrana (Lepidoptera: Tortricidae) at Three Constant Temperatures.

European grapevine moth, Lobesia botrana (Denis and Schiffermüller), is an invasive pest species subject to regulatory control under the International Plant Protection Convention. An extensive infestation of this insect detected in California vineyards in October 2009 resulted in the initiation of postharvest research intended to ensure continuing trade of California table grapes by preventing the unintentional introduction of L. botrana to uninfested export destinations. Having the ability to accurately predict and confirm the particular stadia of larval development of insects obscured from direct observations, such as those being mass-reared in diet for use in phytosanitary control experiments, is necessary to be able to ensure that the most tolerant life stage is accurately targeted. Lobesia botrana were reared from egg to eclosion at three different temperatures: 16, 20, and 24°C (60% RH; 16:8 [L:D] h). Daily samples (≥15) were taken of larvae and pupae to determine the chronological distribution of life stages until daily samples comprised 100% pupae, after which only adults were counted. Head capsule measurements of all sampled larvae were taken (n = 2,820) and analyzed using nonlinear least squares (NLLS) fitting to Gaussian curves to describe stadia-specific head capsule demarcations and the probability of misclassifying instars due to overlapping life stage distributions.

The impact of telephonic wellness coaching on weight loss: A "Natural Experiments for Translation in Diabetes (NEXT-D)" study.

OBJECTIVE: To evaluate the impact of a population-based telephonic wellness coaching program on weight loss. METHODS: Individual-level segmented regression analysis of interrupted time series data comparing the BMI trajectories in the 12 months before versus the 12 months after initiating coaching among a cohort of Kaiser Permanente Northern California members (n = 954) participating in The Permanente Medical Group Wellness Coaching program in 2011. The control group was a 20:1 propensity-score matched control group (n = 19,080) matched with coaching participants based on baseline demographic and clinical characteristics. RESULTS: Wellness coaching participants had a significant upward trend in BMI in the 12 months before their first wellness coaching session and a significant downward trend in BMI in the 12 months after their first session equivalent to a clinically significant reduction of greater than one unit of baseline BMI (P < 0.01 for both). The control group did not have statistically significant decreases in BMI during the post-period. CONCLUSIONS: Wellness coaching has a positive impact on BMI reduction that is both statistically and clinically significant. Future research and quality improvement efforts should focus on disseminating wellness coaching for weight loss in patients with diabetes and those at risk for developing the disease.

Telephone-Based Coaching.

PURPOSE: Many Americans continue to smoke, increasing their risk of disease and premature death. Both telephone-based counseling and in-person tobacco cessation classes may improve access for smokers seeking convenient support to quit. Little research has assessed whether such programs are effective in real-world clinical populations. DESIGN: Retrospective cohort study comparing wellness coaching participants with two groups of controls. SETTING: Kaiser Permanente Northern California, a large integrated health care delivery system. SUBJECTS: Two hundred forty-one patients who participated in telephonic tobacco cessation coaching from January 1, 2011, to March 31, 2012, and two control groups: propensity-score-matched controls, and controls who participated in a tobacco cessation class during the same period. Wellness coaching participants received an average of two motivational interviewing-based coaching sessions that engaged the patient, evoked their reason to consider quitting, and helped them establish a quit plan. MEASURES: Self-reported quitting of tobacco and fills of tobacco cessation medications within 12 months of follow-up. ANALYSIS: Logistic regressions adjusting for age, gender, race/ethnicity, and primary language. RESULTS: After adjusting for confounders, tobacco quit rates were higher among coaching participants vs. matched controls (31% vs. 23%, p < .001) and comparable to those of class attendees (31% vs. 29%, p = .28). Coaching participants and class attendees filled tobacco-cessation prescriptions at a higher rate (47% for both) than matched controls (6%, p < .001). CONCLUSION: Telephonic wellness coaching was as effective as in-person classes and was associated with higher rates of quitting compared to no treatment. The telephonic modality may increase convenience and scalability for health care systems looking to reduce tobacco use and improve health.

Wellness Coaching for People With Prediabetes: A Randomized Encouragement Trial to Evaluate Outreach Methods at Kaiser Permanente, Northern California, 2013.

INTRODUCTION: Health coaching can improve lifestyle behaviors known to prevent or manage chronic conditions. Little is known about effective ways to encourage health and wellness coaching among people who might benefit. The purpose of this randomized encouragement trial was to assess the relative success of 3 outreach methods (secured email message, telephone message, and mailed letter) on the use of wellness coaching by people with prediabetes. METHODS: A total of 14,584 Kaiser Permanente Northern California (KPNC) patients with diagnosed prediabetes (fasting plasma glucose, 110-125mg/dL) were randomly assigned to be contacted via 1 of 4 intervention arms from January through May 2013. The uptake rate (making an appointment at the Wellness Coaching Center [WCC]) was assessed, and the association between uptake rate and patient characteristics was examined via multivariable logistic regression. RESULTS: The overall uptake rate across intervention arms was 1.9%. Secured email message had the highest uptake rate (3.0%), followed by letters and telephone messages (P < .05 for all pairwise comparisons). No participants in the usual-care arm (ie, no outreach) made an appointment with the WCC. For each year of increased age, the estimated odds of the uptake increased by 1.02 (odds ratio [OR] = 1.02; 95% CI, 1.01-1.04). Women were nearly twice as likely to make an appointment at the WCC as men (OR = 1.87; 95% CI, 1.40-2.51). CONCLUSION: Our results suggest that the WCC can recruit and encourage KPNC members with prediabetes to participate in the WCC. Future research should focus on increasing participation rates in health coaching among patients who may benefit.

Reciprocal cellular cross-talk within the tumor microenvironment promotes oncolytic virus activity.

Tumors are complex ecosystems composed of networks of interacting 'normal' and malignant cells. It is well recognized that cytokine-mediated cross-talk between normal stromal cells, including cancer-associated fibroblasts (CAFs), vascular endothelial cells, immune cells, and cancer cells, influences all aspects of tumor biology. Here we demonstrate that the cross-talk between CAFs and cancer cells leads to enhanced growth of oncolytic virus (OV)-based therapeutics. Transforming growth factor-ß (TGF-ß) produced by tumor cells reprogrammed CAFs, dampened their steady-state level of antiviral transcripts and rendered them sensitive to virus infection. In turn, CAFs produced high levels of fibroblast growth factor 2 (FGF2), initiating a signaling cascade in cancer cells that reduced retinoic acid-inducible gene I (RIG-I) expression and impeded the ability of malignant cells to detect and respond to virus. In xenografts derived from individuals with pancreatic cancer, the expression of FGF2 correlated with the susceptibility of the cancer cells to OV infection, and local application of FGF2 to resistant tumor samples sensitized them to virotherapy both in vitro and in vivo. An OV engineered to express FGF2 was safe in tumor-bearing mice, showed improved therapeutic efficacy compared to parental virus and merits consideration for clinical testing.

Activated carbons from end-products of tree nut and tree fruit production as sorbents for removing methyl bromide in ventilation effluent following postharvest chamber fumigation.

End-products of tree nuts and tree fruits grown in California, USA were evaluated for the ability to remove methyl bromide (MB) from ventilation effluent following postharvest chamber fumigation. Activated carbon sorbents from walnut and almond shells as well as peach and prune pits were prepared using different methods of pyrolysis, activation, and quenching. Each source and preparation was evaluated for yield from starting material (%, m/m) and performance on tests where MB-containing airstreams were directed through a columnar bed of the activated carbon in an experimental apparatus, termed a parallel adsorbent column tester, which was constructed as a scaled-down model of a chamber ventilation system. We report the number of doses needed to first observe the breakthrough of MB downstream of the bed and the capacity of the activated carbon for MB (%, m/m) based on a fractional percentage of MB mass sorbed at breakthrough relative to mass of the bed prior to testing. Results were based on a novel application of solid-phase microextraction with time-weighted averaging sampling of MB concentration in airstreams, which was quantitative across the range of fumigation-relevant conditions and statistically unaffected by relative humidity. Activated carbons from prune pits, prepared either by steam activation or carbon dioxide activation coupled to water quenching, received the greatest number of doses prior to breakthrough and had the highest capacity, approximately 12-14%, outperforming a commercially marketed activated carbon derived from coconut shells. Experimental evidence is presented that links discrepancy in performance to the relative potential for activated carbons to preferentially sorb water vapor relative to MB.

Betaine and Trimethylamine-N-Oxide as Predictors of Cardiovascular Outcomes Show Different Patterns in Diabetes Mellitus: An Observational Study.

BACKGROUND: Betaine is a major osmolyte, also important in methyl group metabolism. Concentrations of betaine, its metabolite dimethylglycine and analog trimethylamine-N-oxide (TMAO) in blood are cardiovascular risk markers. Diabetes disturbs betaine: does diabetes alter associations between betaine-related measures and cardiovascular risk? METHODS: Plasma samples were collected from 475 subjects four months after discharge following an acute coronary admission. Death (n = 81), secondary acute MI (n = 87), admission for heart failure (n = 85), unstable angina (n = 72) and all cardiovascular events (n = 283) were recorded (median follow-up: 1804 days). RESULTS: High and low metabolite concentrations were defined as top or bottom quintile of the total cohort. In subjects with diabetes (n = 79), high plasma betaine was associated with increased frequencies of events; significantly for heart failure, hazard ratio 3.1 (1.2-8.2) and all cardiovascular events, HR 2.8 (1.4-5.5). In subjects without diabetes (n = 396), low plasma betaine was associated with events; significantly for secondary myocardial infarction, HR 2.1 (1.2-3.6), unstable angina, HR 2.3 (1.3-4.0), and all cardiovascular events, HR 1.4 (1.0-1.9). In diabetes, high TMAO was a marker of all outcomes, HR 2.7 (1.1-7.1) for death, 4.0 (1.6-9.8) for myocardial infarction, 4.6 (2.0-10.7) for heart failure, 9.1 (2.8-29.7) for unstable angina and 2.0 (1.1-3.6) for all cardiovascular events. In subjects without diabetes TMAO was only significant for death, HR 2.7 (1.6-4.8) and heart failure, HR 1.9 (1.1-3.4). Adding the estimated glomerular filtration rate to Cox regression models tended to increase the apparent risks associated with low betaine. CONCLUSIONS: Elevated plasma betaine concentration is a marker of cardiovascular risk in diabetes; conversely low plasma betaine concentrations indicate increased risk in the absence of diabetes. We speculate that the difference reflects control of osmolyte retention in tissues. Elevated plasma TMAO is a strong risk marker in diabetes.

Patient satisfaction and perceived success with a telephonic health coaching program: the Natural Experiments for Translation in Diabetes (NEXT-D) Study, Northern California, 2011.

INTRODUCTION: Health coaching can improve lifestyle behaviors known to prevent or manage chronic conditions such as diabetes. However, little is known about the patient experience with telephonic coaching programs in real-world care settings. We examined patient satisfaction, patient's perceived success in achieving program goals, and the patient-level correlates of these outcomes in a voluntary telephonic coaching program at a large integrated health care delivery system in northern California. METHODS: Kaiser Permanente Northern California patients who participated in a telephonic coaching program in 2011 were sent a cross-sectional survey about their satisfaction with health coaching and perceived success with program goals. We examined associations with patient characteristics. RESULTS: The survey response rate was 34%; analyses were based on the 32% who completed the survey. Of those who had completed 2 or more sessions (n = 232 [52%]), most reported being satisfied (70%) or neutral (20%) with the program, and 71% would recommend health coaching. Healthy weight, healthful eating, and physical activity were the most common topics discussed (88%). Adjusting for demographic characteristics, 73% of those who had 2 or more sessions reported that health coaching helped achieve their weight-related goal. Outcomes were positively correlated with patient activation but not consistently correlated with patient demographic characteristics. CONCLUSION: Levels of satisfaction and perceived success with telephonic health coaching provided by a health plan were high and positively correlated with the number of sessions completed and patient activation. Voluntary telephonic health coaching programs should promote retention and assess patients' activation levels.

Postharvest treatment of fresh fruit from California with methyl bromide for control of light brown apple moth (Lepidoptera: Tortricidae).

Methyl bromide (MB) chamber fumigations were evaluated for postharvest control of light brown apple moth, Epiphyas postvittana (Walker) (Lepidoptera: Tortricidae), in fresh fruit destined for export from California. To simulate external feeding, larvae were contained in gas-permeable cages and distributed throughout loads of peaches, plums, nectarines (all Prunus spp.), apples (Malus spp.), raspberries (Rubus spp.), or grapes (Vitis spp.). Varying the applied MB dose and the differential sorption of MB by the loads resulted in a range of exposures, expressed as concentration x time cross products (CTs) that were verified by gas-chromatographic quantification of MB in chamber headspace over the course of each fumigation. CTs > or = 60 and > or = 72 mg liter(-1) h at 10.0 +/- 0.5 and 15.6 +/- 0.5 degrees C (x +/- s, average +/- SD), respectively, yielded complete mortality of approximately 6,200 larvae at each temperature. These confirmatory fumigations corroborate E. postvittana mortality data for the first time in relation to measured MB exposures and collectively comprise the largest number of larval specimens tested to date. In addition, akinetic model of MB sorption was developed for the quarantine fumigation of fresh fruit based on the measurement of exposures and how they varied across the fumigation trials. The model describes how to manipulate the applied MB dose, the load factor, and the load geometry for different types of packaged fresh fruit so that the resultant exposure is adequate for insect control.

Quantifying host potentials: indexing postharvest fresh fruits for spotted wing Drosophila, Drosophila suzukii.

Novel methodology is presented for indexing the relative potential of hosts to function as resources. A Host Potential Index (HPI) was developed as a practical framework to express relative host potential based on combining results from one or more independent studies, such as those examining host selection, utilization, and physiological development of the organism resourcing the host. Several aspects of the HPI are addressed including: 1) model derivation; 2) influence of experimental design on establishing host rankings for a study type (no choice, two-choice, and multiple-choice); and, 3) variable selection and weighting associated with combining multiple studies. To demonstrate application of the HPI, results from the interactions of spotted wing drosophila (SWD), Drosophila suzukii Matsumura (Diptera: Drosophilidae), with seven "reported" hosts (blackberries, blueberries, sweet cherries, table grapes, peaches, raspberries, and strawberries) in a postharvest scenario were analyzed. Four aspects of SWD-host interaction were examined: attraction to host volatiles; population-level oviposition performance; individual-level oviposition performance; and key developmental factors. Application of HPI methodology indicated that raspberries ( (mean)HPIvaried  = 301.9±8.39; rank 1 of 7) have the greatest potential to serve as a postharvest host for SWD relative to the other fruit hosts, with grapes ( (mean)HPIvaried  = 232.4±3.21; rank 7 of 7) having the least potential.

The UK General Practice Airways Group (GPIAG): its formation, development, and influence on the management of asthma and other respiratory diseases over the last twenty years.

This article describes the formation and development of the UK General Practice Airways Group (GPIAG), from its inception as a small respiratory special-interest group founded by six general practitioners in 1987 through to its transformation into the largest primary care specialist society in the UK. It highlights the historical context in which the GPIAG was founded - at a time when there was increasing concern about under-treatment and under-diagnosis of asthma in primary care - and describes the way in which its foundation was one of the major influences that led to profound innovation in the primary care management of respiratory disease as well as changes across the primary/secondary care interface. The GPIAG is now a registered charity, has an expanding membership, and has acquired a high profile both nationally and internationally as an advisory body on policy and strategy for the management of respiratory disease in primary care. This review is a 20th anniversary tribute not only to those who have contributed to the success of the GPIAG over the last twenty years, but also to its current membership who enable the GPIAG to continue working towards its charitable aim of "optimal respiratory care for all."

Field and laboratory evaluation of persistence and bioavailability of soil termiticides to desert subterranean termite Heterotermes aureus (Isoptera: Rhinotermitidae).

Control information for the desert subterranean termite Heterotermes aureus (Snyder) (Isoptera: Rhinotermitidae) is limited, despite being one of three major termite pests in the United States. Annual control information comes from field evaluations by the USDA-Forest Service. This partial assessment of termiticide efficacy is likely deficient without concurrent residual analysis and laboratory bioassays of termiticides. In this study, six termiticides were evaluated using exposed and covered field plots in Tucson, AZ, over a 5-yr period for persistence and efficacy by using both residue analysis and laboratory bioassays. All the termiticides degraded significantly during the study. Termiticide degradation seemed to be consistently slower in covered plots than in exposed plots, although this trend was not statistically supported. A comparison of yearly degradation rates showed the three classes of termiticides degraded at different rates. Chlorpyrifos, the organophosphate, degraded quickest at a rate of 68.9% for each doubling of time, whereas chloronicotinyls and pyrethroids degraded at much slower rates (50.4 and 48.4% for each doubling of time, respectively). Bioassays showed termites tunneled 1.26 +/- 0.61 cm deeper in uncovered plots than in those that were covered. Mortality rates in bioassays from covered treatments were 16.13 +/- 9.87% higher than in uncovered treatments. Our study demonstrated that the termiticides evaluated could remain effective against H. aureus for at least 4 yr after application, particularly under covered conditions. Additionally, it is anticipated that retreatments may be necessary before the 5-yr warranty expires when using final grade applications to stem walls in warmer parts of Arizona.

International Primary Care Respiratory Group (IPCRG) Guidelines: management of chronic obstructive pulmonary disease (COPD).

COPD is a common and under-diagnosed disease which is increasing in prevalence worldwide. A more aggressive and optimistic approach must be adopted towards its management in primary care. This IPCRG Guideline on the management of COPD in primary care is fully consistent with GOLD guidelines. It highlights the goals of COPD treatment and the need for spirometric testing to make the diagnosis. It covers the classification of the disease according to disease severity, non-pharmacologic therapy including smoking cessation, avoidance of risk factors, patient education, pharmacologic therapy including the use of oxygen treatment, the management of exacerbations, the role of pulmonary rehabilitation, and the need for monitoring and ongoing care for COPD patients.