Quantifying the impact of interventions against Plasmodium vivax: A model for country-specific use.

In order to evaluate the impact of various intervention strategies on Plasmodium vivax dynamics in low endemicity settings without significant seasonal pattern, we introduce a simple mathematical model that can be easily adapted to reported case numbers similar to that collected by surveillance systems in various countries. The model includes case management, vector control, mass drug administration and reactive case detection interventions and is implemented in both deterministic and stochastic frameworks. It is available as an R package to enable users to calibrate and simulate it with their own data. Although we only illustrate its use on fictitious data, by simulating and comparing the impact of various intervention combinations on malaria risk and burden, this model could be a useful tool for strategic planning, implementation and resource mobilization.

Improved sub-milimeter range-verification method for proton therapy using a composite hadron tumour marker (HTM).

Objective.The results of a follow-up experiment investigating a novel method for sub-milimetre range verification (RV) in proton therapy (PT) are presented.Approach.The method consists of implanting a hadron tumour marker (HTM) near the planned treatment volume, and measuring theγ-ray signals emitted as a result of activation by the proton beam. These signals are highly correlated with the energy of the beam impinging on the HTM and can provide an absolute measurement of the range of the beam relative to the position of the HTM, which is independent of any uncertainties in beam delivery.Main results.Three candidate HTM materials were identified and combined into a single composite HTM, which makes use of the strongest reaction in each material. The setup of the previous experiment was improved on by using high-purity germanium detectors to measure theγ-ray signal with a higher resolution than was previously achieved. A PMMA phantom was also used to simulate theγ-ray background from tissue activation. HTM RV using the data collected in this study yielded range measurements whose average deviation from the expected value was 0.13(22)mm.Significance.Range uncertainty in PT limits the prescribed treatment plan for cancer patients with large safety margins and constrains the direction of the proton beam in relation to any organ at risk. The sub-milimetre range uncertainty achieved in this study using HTM RV, if implemented clinically, would allow for a reduction in the size of safety margins, increasing the therapeutic window for PT.

Oncology clinical trial disruption during the COVID-19 pandemic: a COVID-19 and cancer outcomes study.

BACKGROUND: COVID-19 disproportionately impacted patients with cancer as a result of direct infection, and delays in diagnosis and therapy. Oncological clinical trials are resource-intensive endeavors that could be particularly susceptible to disruption by the pandemic, but few studies have evaluated the impact of the pandemic on clinical trial conduct. PATIENTS AND METHODS: This prospective, multicenter study assesses the impact of the pandemic on therapeutic clinical trials at two large academic centers in the Northeastern United States between December 2019 and June 2021. The primary objective was to assess the enrollment on, accrual to, and activation of oncology therapeutic clinical trials during the pandemic using an institution-wide cohort of (i) new patient accruals to oncological trials, (ii) a manually curated cohort of patients with cancer, and (ii) a dataset of new trial activations. RESULTS: The institution-wide cohort included 4756 new patients enrolled to clinical trials from December 2019 to June 2021. A major decrease in the numbers of new patient accruals (-46%) was seen early in the pandemic, followed by a progressive recovery and return to higher-than-normal levels (+2.6%). A similar pattern (from -23.6% to +30.4%) was observed among 467 newly activated trials from June 2019 to June 2021. A more pronounced decline in new accruals was seen among academically sponsored trials (versus industry sponsored trials) (P < 0.05). In the manually curated cohort, which included 2361 patients with cancer, non-white patients tended to be more likely taken off trial in the early pandemic period (adjusted odds ratio: 2.60; 95% confidence interval 1.00-6.63), and substantial pandemic-related deviations were recorded. CONCLUSIONS: Substantial disruptions in clinical trial activities were observed early during the pandemic, with a gradual recovery during ensuing time periods, both from an enrollment and an activation standpoint. The observed decline was more prominent among academically sponsored trials, and racial disparities were seen among people taken off trial.

Frontal fibrosing alopecia: survey of severity assessment methods in routine clinical practice and validation of the International Frontal Fibrosing Alopecia Cooperative Group measurement guidance.

BACKGROUND: The lack of validated and responsive outcome measures in the management of frontal fibrosing alopecia (FFA) significantly limits assessment of disease progression and treatment response over time. AIM: To understand how FFA extent and progression is currently assessed in UK specialist centres, to validate components of the International FFA Cooperative Group (IFFACG) statement on FFA assessment, and to identify pragmatic advice to improve FFA management in clinic. METHODS: Consultant dermatologists with a specialist interest in hair loss (n = 17) were invited to take part. Preferred FFA assessment methods were explored using questionnaires and clinical scenarios. Participants were asked to identify and mark the current hairline in 10 frontal and 10 temporal hairline images (Questionnaire 1), with assessment repeated 3 months later to assess intraindividual variability (Questionnaire 2) and 12 months later to test whether interindividual accuracy could be improved with simple instruction (Questionnaire 3). RESULTS: All 17 clinicians (100%) completed the questionnaire at each time interval. We identified a wide variation in assessment techniques used by our experts. Measurements were perceived as the most accurate method of assessing frontal recession whereas photography was preferred for temporal recession. Inter-rater reliability between clinicians measuring the frontal hairline scenarios indicated a moderate strength of agreement [intraclass coefficient (ICC) = 0.61; 95% CI 0.40-0.85], yet intrarater reliability was found to be poor with wide limits of agreement (-8.71 mm to 9.92 mm) on follow-up. Importantly, when clear guidance was provided on how the hairline should be identified (Questionnaire 3), inter-rater reliability improved significantly, with ICC = 0.70, suggesting moderate agreement (95% CI 0.51-0.89; P < 0.001). A similar pattern was seen with temporal hairline measurements, which again improved in accuracy with instruction. CONCLUSION: We found that accuracy of measurements in FFA can be improved with simple instruction and we have validated components of the IFFACG measurement recommendations.

Influence of season, age, sex, and time of day on the endocrine profile of the common bottlenose dolphin (Tursiops truncatus).

Understanding baseline hormone levels, the magnitude of intra-individual variability, and their variation as a function of life history is difficult in toothed whales (e.g. dolphins and porpoises) because of the effects of capture stress. To determine the endocrine profile of the common bottlenose dolphin (Tursiops truncatus) as a function of season, time of day (TOD), age, sex, and reproductive status, blood corticosteroids, thyroid hormones, and catecholamines were repeatedly measured in a managed-care population exposed to ambient light and water temperatures of San Diego Bay. Additionally, fecal hormone metabolites were assessed for cortisol, aldosterone, and triiodothyronine. Samples were collected at two to four-week intervals over a period of two years, and multiple times within a day at monthly intervals over a year. Samples were collected through the voluntary participation of the dolphins in the blood draws and fecal collections in order to avoid the effects of handling stress. All serum hormones except aldosterone significantly varied with season and all serum hormones except total thyroxine significantly varied as a function of TOD. Fecal glucocorticoid metabolites significantly correlated with circulating cortisol levels, and there was a significant seasonal effect on triiodothyronine fecal metabolites. Strong seasonal effects demonstrated complex interactions with age and sex suggesting that contextual information is critical to interpreting differences in endocrine profiles. Strong circadian patterns further suggest that sampling design is important to the interpretation of blood or fecal collections, particularly since diurnal changes in some serum hormone levels are similar to the magnitude of seasonal differences. Despite potential impacts of feeding schedules on diurnal patterns, managed care populations can provide important insights into seasonal and age-related endocrine changes in toothed whales.

Facilitators and barriers to the use of service dogs: an exploratory study using the Theoretical Domains Framework.

Purpose: Given the scarcity of service dogs to help individuals with mobility impairments in the community, it is crucial to identify facilitators and obstacles to the acquisition and use of service dogs in order to optimize their use and have a positive impact on the lives of individuals with disabilities. The goal of this study was to describe perceived facilitators and barriers influencing the acquisition and use of service dog by owners and rehabilitation providers, including those who had and had not recommended service dogs.Method: We conducted a phenomenological qualitative study involving in-depth interviews with nine service dog owners and 13 rehabilitation professionals in Canada. Our questionnaires were based on the Theoretical Domains Framework and the data were analyzed using a thematic content approach.Results: Knowledge, beliefs about consequences, and environmental context and resources were the domains most frequently mentioned by both dog owners and rehabilitation professionals. While service dog owners placed greater importance on their belief in their capacity to get and use service dogs, rehabilitation professionals focussed more on their role and identity within the process.Conclusion: Improving the knowledge of the availability and process of acquiring service dogs would be important for rehabilitation professions to improve the quality of life and functional capabilities of persons with disabilities.Implications for rehabilitationIdentifying determinants of service dog acquisition and use can support proposed strategies to optimize the use of this assistive technology;Determinants of service dog acquisition and use are are different for dog owners and rehabilitation professionals, which suggest the need of tailored knowledge translation strategies;Knowledge, beliefs about consequences, and environmental context and resources were the categories of determinants perceived as being more influential on the process.

[Technique of complex mammary irradiation: Mono-isocentric 3D conformational radiotherapy and helical tomotherapy]. / Techniques d'irradiation mammaire complexe : radiothérapie conformationelle tridimensionnelle mono-isocentrique et nomothérapie hélicoïdale.

PURPOSE: To evaluate the dosimetric contribution of helical tomotherapy for breast cancers compared with conformal radiotherapy in mono-isocentric technique. PATIENTS AND METHOD: For 23 patients, the dosimetric results in mono-isocentric 3D conformational radiotherapy did not satisfy the constraints either of target volumes nor organs at risk. A prospective dosimetric comparison between mono-isocentric 3D conformational radiotherapy and helical tomotherapy was therefore carried out. RESULTS: The use of helical tomotherapy showed a benefit in these 23 patients, with either an improvement in the conformity index or homogeneity, but with an increase in low doses. Of the 23 patients, two had pectus excavatum, five had past thoracic irradiation and two required bilateral irradiation. The other 14 patients had a combination of morphology and/or indication of lymph node irradiation. For these patients, helical tomotherapy was therefore preferred to mono-isocentric 3D conformational radiotherapy. CONCLUSIONS: Tomotherapy appears to provide better homogeneity and tumour coverage. This technique of irradiation may be justified in the case of morphological situations such as pectus exavatum and in complex clinical situations. In other cases, conformal radiotherapy in mono-isocentric technique remains to be favoured.

Markers of dietary protein intake are associated with successful weight loss in the POUNDS Lost trial.

To assess the association of markers for dietary protein intake, measures of dietary adherence and demographic variables with weight loss in the POUNDS Lost study over the first 6 months and again between 6 and 24 months using data from those who completed each period. This is a secondary analysis of pooled data on completers assigned to one of four diets: 65%C/15%P/20%F (AP/LF), 55%C/25%P/20%F (HP/LF), 45%C/15%P/40%F (AP/HF) or 35%C/25%P40%F (HP/HF) in the POUNDS Lost study. Urinary nitrogen excretion, dietary adherence measured by 24-h recall and attendance at sessions, age (above and below 50 years), gender, race/ethnicity and activity by pedometry were analysed. Increased spread between protein intake at baseline and protein at 6 or 24 months, assessed by urinary nitrogen excretion, was associated with greater weight loss from baseline to 2 years. At 6 and 24 months, older age, male gender, body mass index > 30 kg m-2 and adherence to the fat and protein diets were associated with more weight loss. None of these variables was associated with a regain from 6 to 24 months. Weight regain for women in the highest carbohydrate (65%) group was significantly greater (-4.4 kg [95% CI: -5.9, -3.0]) than for women in the lowest carbohydrate group (-1.8 kg [95% CI: -3.2, -0.4 kg]) (P for interaction = 0.012). An increased spread in the difference between baseline and follow-up protein intake was associated with greater weight loss, consistent with the 'protein spread theory'. Women eating the highest carbohydrate diet regained more weight from 6 to 24 months.

Blubber transcriptome response to acute stress axis activation involves transient changes in adipogenesis and lipolysis in a fasting-adapted marine mammal.

Stress can compromise an animal's ability to conserve metabolic stores and participate in energy-demanding activities that are critical for fitness. Understanding how wild animals, especially those already experiencing physiological extremes (e.g. fasting), regulate stress responses is critical for evaluating the impacts of anthropogenic disturbance on physiology and fitness, key challenges for conservation. However, studies of stress in wildlife are often limited to baseline endocrine measurements and few have investigated stress effects in fasting-adapted species. We examined downstream molecular consequences of hypothalamic-pituitary-adrenal (HPA) axis activation by exogenous adrenocorticotropic hormone (ACTH) in blubber of northern elephant seals due to the ease of blubber sampling and its key role in metabolic regulation in marine mammals. We report the first phocid blubber transcriptome produced by RNAseq, containing over 140,000 annotated transcripts, including metabolic and adipocytokine genes of interest. The acute response of blubber to stress axis activation, measured 2 hours after ACTH administration, involved highly specific, transient (lasting <24 hours) induction of gene networks that promote lipolysis and adipogenesis in mammalian adipocytes. Differentially expressed genes included key adipogenesis factors which can be used as blubber-specific markers of acute stress in marine mammals of concern for which sampling of other tissues is not possible.

Endoscopic septoplasty: Learning curve.

AIMS: The aim of the current study was to report the learning curve for endoscopic septoplasty for a senior surgeon already trained in endonasal sinus surgery. MATERIAL AND METHODS: From November 2011 to September 2012, 100 patients were prospectively included and grouped in 5 consecutive groups of 20 by date of surgery. The primary endpoint was operative time. Intra- and postoperative complications and functional assessment were also analyzed. RESULTS: Operative time decreased with the surgeon's experience and became stable after 60 procedures. Operative time saving was about 10min per 20 procedures. Mean operative time was stable between groups 4 (21.1±9.6min) and 5 (19.2±8.2min). There was a 2% rate of conversion to conventional surgery for technical problems. The number of procedures free of accidental mucosal lesion increased and became stable after 40 procedures. There was a 4% rate of residual postoperative perforation. Nasal Obstruction and Septoplasty Effectiveness (NOSE) score improved postoperatively in each group (P<0.05). CONCLUSION: After 60 endoscopic septoplasty procedures, a senior surgeon masters the surgical technique with satisfactory operative times, and a decreasing rate of intra- and postoperative complications.

Endoscopic vs. conventional septoplasty: A review of the literature.

The aim of this review of literature was to compare conventional and endoscopic septoplasty in terms of operating time, functional efficacy and perioperative morbidity. A systematic review of the scientific literature was performed on the PubMed database, Google and Google Scholar, searching for randomized prospective trials comparing endoscopic and conventional septoplasty. The primary endpoint was operating time, and the secondary endpoints were intra- and postoperative complications, postoperative pain, hospital stay and functional result. Twenty-nine articles published between 1991 and 2012 compared conventional and endoscopic septoplasty, five of which were prospective randomized trials. Operating time was shorter with endoscopic surgery (P<0.001), with less mucosal damage (P<0.01); there was less synechia (P<0.01) and residual deformity (P<0.05); and postoperative pain was milder. Endoscopic septoplasty thus shortened surgery time and reduced perioperative complications, but the functional result was the same as with conventional septoplasty.

A critical role for cellular inhibitor of protein 2 (cIAP2) in colitis-associated colorectal cancer and intestinal homeostasis mediated by the inflammasome and survival pathways.

Cellular inhibitors of apoptosis proteins (cIAPs) are critical arbiters of cell death and key mediators of inflammation and innate immunity. cIAP2 is frequently overexpressed in colorectal cancer and in regenerating crypts of ulcerative colitis patients. However, its corresponding functions in intestinal homeostasis and underlying mechanisms in disease pathogenesis are poorly understood. We found that mice deficient in cIAP2 exhibited reduced colitis-associated colorectal cancer tumor burden but, surprisingly, enhanced susceptibility to acute and chronic colitis. The exacerbated colitis phenotype of cIAP2-deficient mice was mediated by increased cell death and impaired activation of the regenerative inflammasome-interleukin-18 (IL-18) pathway required for tissue repair following injury. Accordingly, administration of recombinant IL-18 or pharmacological inhibition of caspases or the kinase RIPK1 protected cIAP2-deficient mice from colitis and restored intestinal epithelial barrier architecture. Thus, cIAP2 orchestrates intestinal homeostasis by exerting a dual function in suppressing cell death and promoting intestinal epithelial cell proliferation and crypt regeneration.

Psychosocial predictors of weight loss by race and sex.

This paper examined the psychosocial predictors of weight loss among race and sex subgroups. Analyses included overweight and obese participants from the PREMIER study, a previously published randomized trial that examined the effects of two multi-component lifestyle interventions on blood pressure among pre-hypertensive and stage 1 hypertensive adults. Both intervention conditions received behavioural recommendations for weight loss and group sessions. Weight and psychosocial measures of self-efficacy and social support for diet and exercise were assessed at baseline and at 6 months. There were 157 African-American (AA) women, 46 AA men, 203 non-AA women and 182 non-AA men with an average age of 50 years and average body mass index of 34 at baseline. Multiple predictor regression models were performed individually by race and sex subgroup. Among AA women, increases in diet self-efficacy were associated with weight loss. Among AA men, increases in diet-related social support and self-efficacy, along with increases in family support to exercise, were associated with weight loss (all Ps <0.05). Among non-AA women, increases in friends' support to exercise and exercise-related self-efficacy were associated with weight loss, and among non-AA men only increases in diet self-efficacy were associated with weight loss (all Ps <0.05). These results emphasize the need for targeted interventions based on race and sex to optimize the impact of lifestyle-based weight loss programmes.

Endoscopic septoplasty: Tips and pearls.

This article is designed to provide a step-by-step description of our endoscopic septoplasty technique and discuss its difficulties and technical tips. Endoscopic septoplasty comprises 10 steps: diagnostic endoscopy, subperichondral infiltration, left mucosal incision, dissection of the left subperichondral flap, cartilage incision (0.5 centimetre posterior to the mucosal incision), dissection of the right subperichondral flap, anterior cartilage resection, perpendicular plate dissection, dissection and resection of the maxillary crest, endoscopic revision, mucosal suture and Silastic stents. A satisfactory postoperative result was observed at 3 months in 97% of cases in this series. The main contraindication to endoscopic septoplasty is anterior columellar deviation of the nasal septum requiring a conventional procedure.

Impact of a yogurt matrix and cell microencapsulation on the survival of Lactobacillus reuteri in three in vitro gastric digestion procedures.

The goal of this study was to assess the interaction between microencapsulation and a yogurt food matrix on the survival of Lactobacillus reuteri NCIMB 30242 in four different in vitro systems that simulate a gastric environment. The four systems were: United States Pharmacopeia (USP) solutions, a static two-step (STS) procedure which included simulated food ingredients, a constantly dynamic digestion procedure (IViDiS), as well a multi-step dynamic digestion scheme (S'IViDiS). The pH profiles of the various procedures varied between systems with acidity levels being: USP > STS > IViDiS = S'IVIDiS. Addition of a food matrix increased the pH in all systems except for the USP methodology. Microencapsulation in alginate-based gels was effective in protecting the cells in model solutions when no food ingredients were present. The stability of the probiotic culture in the in vitro gastric environments was enhanced when (1) yoghurt or simulated food ingredient were present in the medium in sufficient quantity, (2) pH was higher. The procedure-comparison data of this study will be helpful in interpreting the literature with respect to viable counts of probiotics obtained from different static or dynamic in vitro gastric systems.

An international comparison of dietary patterns in 9-11-year-old children.

OBJECTIVES: Dietary pattern is defined as a combination of foods and drinks and the frequency of consumption within a population. Dietary patterns are changing on a global level, which may be linked to an increased incidence of chronic diseases. The aim of this study was to identify and compare the dietary patterns among 9-11-year-old children living in urban regions in different parts of the world. METHODS: Participants were 7199 children (54% girls), aged 9-11 years, from 12 countries situated in all major world regions. Food consumption was assessed using a 23-item Food Frequency Questionnaire (FFQ). To identify dietary patterns, principal components analyses (PCA) were carried out using weekly portions as input variables. RESULTS: Both site-specific and pooled PCA resulted in two strong components. Component 1 ('unhealthy diet pattern') included fast foods, ice cream, fried food, French fries, potato chips, cakes and sugar-sweetened sodas with >0.6 loadings. The loadings for component 2 ('healthy diet pattern') were slightly weaker with only dark-green vegetables, orange vegetables, vegetables in general, and fruits and berries reaching a >0.6 loading. The site-specific diet pattern scores had very strong correlations with the pattern scores from the pooled data: r=0.82 and 0.94 for components 1 and 2, respectively. CONCULSIONS: The results suggest that the same 'healthier' and 'unhealthier' foods tend to be consumed in similar combinations among 9-11-year-old children in different countries, despite variation in food culture, geographical location, ethnic background and economic development.

The reliability and validity of a short food frequency questionnaire among 9-11-year olds: a multinational study on three middle-income and high-income countries.

OBJECTIVE: The main aim of this study was to assess the reliability and validity of a food frequency questionnaire with 23 food groups (I-FFQ) among a sample of 9-11-year-old children from three different countries that differ on economical development and income distribution, and to assess differences between country sites. Furthermore, we assessed factors associated with I-FFQ's performance. METHODS: This was an ancillary study of the International Study of Childhood Obesity, Lifestyle and the Environment. Reliability (n=321) and validity (n=282) components of this study had the same participants. Participation rates were 95% and 70%, respectively. Participants completed two I-FFQs with a mean interval of 4.9 weeks to assess reliability. A 3-day pre-coded food diary (PFD) was used as the reference method in the validity analyses. Wilcoxon signed-rank tests, intraclass correlation coefficients and cross-classifications were used to assess the reliability of I-FFQ. Spearman correlation coefficients, percentage difference and cross-classifications were used to assess the validity of I-FFQ. A logistic regression model was used to assess the relation of selected variables with the estimate of validity. Analyses based on information in the PFDs were performed to assess how participants interpreted food groups. RESULTS: Reliability correlation coefficients ranged from 0.37 to 0.78 and gross misclassification for all food groups was <5%. Validity correlation coefficients were below 0.5 for 22/23 food groups, and they differed among country sites. For validity, gross misclassification was <5% for 22/23 food groups. Over- or underestimation did not appear for 19/23 food groups. Logistic regression showed that country of participation and parental education were associated (P⩽0.05) with the validity of I-FFQ. Analyses of children's interpretation of food groups suggested that the meaning of most food groups was understood by the children. CONCLUSION: I-FFQ is a moderately reliable method and its validity ranged from low to moderate, depending on food group and country site.