Offshore floating wind turbines (OFWTs) present unique aerodynamic analysis challenges. Motion–derived velocity perturbations in the wake necessitate higher–fidelity aerodynamic analysis methods than ...the ubiquitous momentum balance techniques currently in use. A more physically–sound approach is to model the wake generated by a wind turbine rotor as a freely convecting lattice, using the resultant inflow to estimate rotor loads, as it done with a free vortex wake method (FVM). The FVM code Wake Induced Dynamics Simulator (WInDS) was developed at the University of Massachusetts at Amherst to predict the aerodynamic loading and wake evolution of an OFWT to a higher degree of accuracy than is possible via momentum balance methods. A series of validation cases were conducted to provide some basis for applying WInDS to floating wind turbine cases, for which no aerodynamic experimental data is currently available. The results from these tests show that WInDS is able to accurately predict the aerodynamically–derived loads and wake structures generated by various fixed and rotary–wing cases, and may therefore be applied to more complex cases, like OFWTs, with a degree of confidence.
► Developed and tested a free vortex model code (WInDS) for future study of offshore floating wind turbine aerodynamics. ► Described the theory and implementation of the code. ► Validated using test cases, both analytical and experimental. ► WInDS demonstrated robust properties necessary for floating wind turbine simulations.
We provide a general framework for understanding functional gastrointestinal disorders (FGIDs) from a biopsychosocial perspective. More specifically, we provide an overview of the recent research on ...how the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of FGIDs. We emphasize that considering and addressing all these factors is a conditio sine qua non for appropriate treatment of these conditions. First, we provide an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual’s family, the individual’s own psychological states and traits, and the individual’s (neuro)physiological make-up—interact to ultimately result in the generation of FGID symptoms. Second, we provide an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of these factors in their patients. Finally, the broader perspective outlined earlier is applied to provide an overview of centrally acting treatment strategies, both psychological and pharmacological, which have been shown to be efficacious to treat FGIDs.
These European Society for Clinical Microbiology and Infectious Diseases and European Confederation of Medical Mycology Joint Clinical Guidelines focus on the diagnosis and management of ...mucormycosis. Only a few of the numerous recommendations can be summarized here. To diagnose mucormycosis, direct microscopy preferably using optical brighteners, histopathology and culture are strongly recommended. Pathogen identification to species level by molecular methods and susceptibility testing are strongly recommended to establish epidemiological knowledge. The recommendation for guiding treatment based on MICs is supported only marginally. Imaging is strongly recommended to determine the extent of disease. To differentiate mucormycosis from aspergillosis in haematological malignancy and stem cell transplantation recipients, identification of the reverse halo sign on computed tomography is advised with moderate strength. For adults and children we strongly recommend surgical debridement in addition to immediate first-line antifungal treatment with liposomal or lipid-complex amphotericin B with a minimum dose of 5 mg/kg/day. Amphotericin B deoxycholate is better avoided because of severe adverse effects. For salvage treatment we strongly recommend posaconazole 4 × 200 mg/day. Reversal of predisposing conditions is strongly recommended, i.e. using granulocyte colony-stimulating factor in haematological patients with ongoing neutropenia, controlling hyperglycaemia and ketoacidosis in diabetic patients, and limiting glucocorticosteroids to the minimum dose required. We recommend against using deferasirox in haematological patients outside clinical trials, and marginally support a recommendation for deferasirox in diabetic patients. Hyperbaric oxygen is supported with marginal strength only. Finally, we strongly recommend continuing treatment until complete response demonstrated on imaging and permanent reversal of predisposing factors.
There is an urgent need for safe treatments for irritable bowel syndrome (IBS) that relieve treatment-refractory symptoms and their societal and economic burden. Cognitive behavior therapy (CBT) is ...an effective treatment that has not been broadly adopted into routine clinical practice. We performed a randomized controlled trial to assess clinical responses to home-based CBT compared with clinic-based CBT and patient education.
We performed a prospective study of 436 patients with IBS, based on Rome III criteria, at 2 tertiary centers from August 23, 2010, through October 21, 2016. Subjects (41.4 ± 14.8 years old; 80% women) were randomly assigned to groups that received the following: standard-CBT (S-CBT, n = 146, comprising 10 weekly, 60-minute sessions that emphasized the provision of information about brain-gut interactions; self-monitoring of symptoms, their triggers, and consequences; muscle relaxation; worry control; flexible problem solving; and relapse prevention training), or 4 sessions of primarily home-based CBT requiring minimal therapist contact (MC-CBT, n = 145), in which patients received home-study materials covering the same procedures as S-CBT), or 4 sessions of IBS education (EDU, n = 145) that provided support and information about IBS and the role of lifestyle factors such as stress, diet, and exercise. The primary outcome was global improvement of IBS symptoms, based on the IBS-version of the Clinical Global Impressions-Improvement Scale. Ratings were performed by patients and board-certified gastroenterologists blinded to treatment allocation. Efficacy data were collected 2 weeks, 3 months, and 6 months after treatment completion.
A higher proportion of patients receiving MC-CBT reported moderate to substantial improvement in gastrointestinal symptoms 2 weeks after treatment (61.0% based on ratings by patients and 55.7% based on ratings by gastroenterologists) than those receiving EDU (43.5% based on ratings patients and 40.4% based on ratings by gastroenterologists) (P < .05). Gastrointestinal symptom improvement, rated by gastroenterologists, 6 months after the end of treatment also differed significantly between the MC-CBT (58.4%) and EDU groups (44.8%) (P = .05). Formal equivalence testing applied across multiple contrasts indicated that MC-CBT is at least as effective as S-CBT in improving IBS symptoms. Patients tended to be more satisfied with CBT vs EDU (P < .05) based on immediate posttreatment responses to the Client Satisfaction Questionnaire. Symptom improvement was not significantly related to concomitant use of medications.
In a randomized controlled trial, we found that a primarily home-based version of CBT produced significant and sustained gastrointestinal symptom improvement for patients with IBS compared with education. Clinicaltrials.gov no.: NCT00738920.
The aetiological agents of many invasive fungal infections are saprobes and opportunistic pathogens. Some of these fungi are darkly pigmented due to melanin production and traditionally have been ...named ‘dematiaceous’. The melanized fungi cause a wide array of clinical syndromes ranging from superficial to deep-seated infections. Diagnosis relies on histopathological examination of clinical specimens and on examination of cultures. Sequencing is recommended for accurate species identification, especially for unusual or newly described pathogens. In cases of mycetoma and chromoblastomycosis, pathognomonic histological findings are useful and the Fontana–Masson stain, specific for melanin, usually confirms the diagnosis. There are no standardized therapies but voriconazole, posaconazole and itraconazole demonstrate the most consistent in vitro activity against this group of fungi. Oral itraconazole has been considered the drug of choice, given the extensive clinical experience with this drug. However, voriconazole may presumably be superior for central nervous system infections because of its ability to achieve good levels in the cerebrospinal fluid. Posaconazole is a well-tolerated alternative drug, backed by less clinical experience but with excellent salvage treatment results after failure of other antifungals. Amphotericin B has been useful as alternative therapy in some cases. Combination antifungal therapy is recommended for cerebral abscesses when surgery is not possible and for disseminated infections in immunocompromised patients.
Abstract
Background
Irritable bowel syndrome (IBS) is a common, often disabling gastrointestinal (GI) disorder for which there is no satisfactory medical treatment but is responsive to cognitive ...behavior therapy (CBT).
Purpose
To evaluate the costs and cost-effectiveness of a minimal contact version of CBT (MC-CBT) condition for N = 145 for IBS relative to a standard, clinic-based CBT (S-CBT; N = 146) and a nonspecific comparator emphasizing education/support (EDU; N = 145).
Method
We estimated the per-patient cost of each treatment condition using an activity-based costing approach that allowed us to identify and estimate costs for specific components of each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of MC-CBT relative to S-CBT and EDU. We then evaluated the cost-effectiveness of MC-CBT relative to these alternatives for selected outcomes at immediate posttreatment and 6 months posttreatment, using both an intent-to-treatment and per-protocol methodology. Key outcomes included scores on the Clinical Global Impressions-Improvement Scale and the percentage of patients who positively responded to treatment.
Results
The average per-patient cost of delivering MC-CBT was $348, which was significantly less than the cost of S-CBT ($644) and EDU ($457) (p < .01). Furthermore, MC-CBT produced better average patient outcomes at immediate and 6 months posttreatment relative to S-CBT and EDU (p < .01). The current findings indicated that MC-CBT is a cost-effective option relative to S-CBT and EDU.
Conclusion
As predicted, MC-CBT was delivered at a lower cost per patient than S-CBT and performed better over time on the primary outcome of global IBS symptom improvement.
A largely home-based regimen of cognitive behavioral therapy for irritable bowel syndrome was delivered at a lower cost per patient than traditional office-based CBT and performed better over time in relieving core gastrointestinal symptoms (e.g., abdominal pain, altered bowel habits such as diarrhea and/or constipation) refractory to conventional medical treatments.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder that is thought to involve alterations in the gut microbiome, but robust microbial signatures have been challenging to identify. ...As prior studies have primarily focused on composition, we hypothesized that multi-omics assessment of microbial function incorporating both metatranscriptomics and metabolomics would further delineate microbial profiles of IBS and its subtypes.
Fecal samples were collected from a racially/ethnically diverse cohort of 495 subjects, including 318 IBS patients and 177 healthy controls, for analysis by 16S rRNA gene sequencing (n = 486), metatranscriptomics (n = 327), and untargeted metabolomics (n = 368). Differentially abundant microbes, predicted genes, transcripts, and metabolites in IBS were identified by multivariate models incorporating age, sex, race/ethnicity, BMI, diet, and HAD-Anxiety. Inter-omic functional relationships were assessed by transcript/gene ratios and microbial metabolic modeling. Differential features were used to construct random forests classifiers.
IBS was associated with global alterations in microbiome composition by 16S rRNA sequencing and metatranscriptomics, and in microbiome function by predicted metagenomics, metatranscriptomics, and metabolomics. After adjusting for age, sex, race/ethnicity, BMI, diet, and anxiety, IBS was associated with differential abundance of bacterial taxa such as Bacteroides dorei; metabolites including increased tyramine and decreased gentisate and hydrocinnamate; and transcripts related to fructooligosaccharide and polyol utilization. IBS further showed transcriptional upregulation of enzymes involved in fructose and glucan metabolism as well as the succinate pathway of carbohydrate fermentation. A multi-omics classifier for IBS had significantly higher accuracy (AUC 0.82) than classifiers using individual datasets. Diarrhea-predominant IBS (IBS-D) demonstrated shifts in the metatranscriptome and metabolome including increased bile acids, polyamines, succinate pathway intermediates (malate, fumarate), and transcripts involved in fructose, mannose, and polyol metabolism compared to constipation-predominant IBS (IBS-C). A classifier incorporating metabolites and gene-normalized transcripts differentiated IBS-D from IBS-C with high accuracy (AUC 0.86).
IBS is characterized by a multi-omics microbial signature indicating increased capacity to utilize fermentable carbohydrates-consistent with the clinical benefit of diets restricting this energy source-that also includes multiple previously unrecognized metabolites and metabolic pathways. These findings support the need for integrative assessment of microbial function to investigate the microbiome in IBS and identify novel microbiome-related therapeutic targets. Video Abstract.
An internet-delivered cognitive behavioral treatment (ICBT) based on systematic exposure exercises has previously shown beneficial effects for patients with irritable bowel syndrome (IBS). Exposure ...exercises may be perceived as difficult for patients to perform because of the elicited short-term distress and clinicians may be reluctant to use these interventions. The aim of this study was to compare ICBT with the same protocol without systematic exposure (ICBT-WE) to assess if exposure had any incremental value. This randomized controlled dismantling study included 309 participants diagnosed with IBS. The treatment interventions lasted for 10 weeks and included online therapist contact. ICBT-WE comprised mindfulness, work with life values, acceptance, and encouraged reduced avoidance behaviors, while ICBT also included systematic exposure to IBS symptoms and related situations. Severity of IBS symptoms was measured with the Gastrointestinal Symptom Rating Scale – IBS version (GSRS-IBS). The between-group Cohen's d on GSRS-IBS was 0.47 (95% CI: 0.23–0.70) at post-treatment and 0.48 (95% CI: 0.20–0.76) at 6-month follow-up, favoring ICBT. We conclude that the systematic exposure included in the ICBT protocol has incremental effects over the other components in the protocol. This study provides evidence for the utility of exposure exercises in psychological treatments for IBS.
•Few psychological treatments for irritable bowel syndrome (IBS) include exposure.•We investigated the effect of exposure exercises for IBS using a dismantling design.•Exposure had an incremental effect compared to mindfulness and values work.•Psychological treatments for IBS may benefit from including exposure exercises.
BAL fluid samples from critically ill patients shared a rate of 29% false-positive galactomannan results. We aimed to determine whether
species abundance in BAL fluid causes galactomannan (GM) ...positivity. A total of 89
culture-positive BAL fluid samples from patients without suspicion of invasive aspergillosis (IA) were analyzed. GM results were correlated with
species abundance,
species quantity, and patient data.
species quantities of ≥10
/ml and
abundance were significantly associated with positive GM results. The added diagnostic value of GM in BAL fluid for diagnosing IA in critically ill patients is limited.
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