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Summary Although the development of psilocybin therapy has come as a surprise to many, modern research with the drug has been ongoing for 25 years. Psilocybin therapy is composed of psilocybin dosing sessions embedded within a wider process of psychoeducation, psychological support and integration. Early phase clinical trial evidence is promising, particularly for treatment-resistant depression. However, masking probably fails and expectancy effects may be a part of the mechanism of change. Disambiguating between drug and expectancy effects is a necessary part of the development process, yet this is difficult if masking fails. Hitherto, masking and expectancy have not been routinely measured in psilocybin or other medication trials. Doing so represents an opportunity for research and may influence psychiatry more widely. In this opinion piece I summarise the clinical development process of psilocybin therapy thus far, discussing the hope, the hype, the challenges and the opportunities along the way.

Attention-deficit hyperactivity disorder (ADHD) is a neurodevelopmental condition that is estimated to affect 5% of children and adolescents worldwide. The core manifestations of ADHD include impulsivity, inattentiveness and hyperactivity, with there being a high proportion of individuals also experiencing other psychiatric co-morbidities. Currently available treatments for ADHD are limited by the low adherence rates related to adverse events. However, it has been suggested that cannabis-based medicinal products (CBMPs) may be effective in the treatment of ADHD, as evidence has shown how cannabis can lead to improvements in symptoms of hyperactivity and impulsivity. However, there is still limited published data supporting its use and further randomised controlled trials are required to help establish the efficacy, safety and exact role of CBMPs for the treatment of ADHD. ADHD patients can be assessed for receiving potential treatment with CBMPs by specialist clinics, such as Sapphire Medical Clinics, in instances where they have failed to respond to their treatment.

Psychedelic therapy shows promise for Major Depressive Disorder, especially when treatment-resistant, as well as life-threatening illness distress. The objective of this systematic review, inclusive of meta-analysis, is to examine recent clinical research on the therapeutic effects of classic psychedelics on depressive symptoms.Fourteen psychedelic therapy studies, utilising psilocybin, ayahuasca, or LSD, were systematically reviewed. For the meta-analysis, standardised mean differences were calculated for seven randomised controlled trials.The systematic review indicated significant short- and long-term reduction of depressive symptoms in all conditions studied after administration of psilocybin, ayahuasca, or LSD, with psychological support. In the meta-analysis, symptom reduction was significantly indicated in three timepoints out of four, including 1-day, 1-week, and 3-5 weeks, supporting the results of the systematic review, with the exception of the 6-8 weeks follow-up point which was less conclusive.The absence of required data for 2 studies necessitated the less precise use of graphical extraction and imputation. The small sample size in all but one study negatively affected the statistical power. None of the studies had long-term follow-up without also utilising the cross-over method, which did not allow for long-term results to be included in the meta-review.This review indicates an association between psychedelic therapy and significant reduction of depressive symptoms at several time points. However, the small number of studies, and low sample sizes, calls for careful interpretation of results. This suggests the need for more randomised clinical trials of psychedelic therapy, with larger and more diverse samples.

Background There is a paucity of high-quality evidence of the efficacy and safety of cannabis-based medicinal products in treatment of treatment-resistant epilepsy (TRE) in children. Methods A case series of children ( Results Thirty-five patients were included in the analysis. Patients were prescribed during their treatment with the following: CBD isolate oils (n = 19), CBD broad-spectrum oils (n = 17), and CBD/Δ9-THC combination therapy (n = 17). Twenty-three (65.7%) patients achieved a ≥50% reduction in seizure frequency. 94.1% (n = 16) of patients treated with CBD and Δ9-THC observed a ≥50% reduction in seizure frequency compared to 31.6% (n = 6) and 17.6% (n = 3) of patients treated with CBD isolates and broad-spectrum CBD products, respectively (p< 0.001). Twenty-six (74.3%) adverse events were reported by 16 patients (45.7%). The majority of these were mild (n = 12; 34.2%) and moderate (n = 10; 28.6%). Conclusion The results of this study demonstrate a positive signal of improved seizure frequency in children treated with Cannabis-based medicinal products (CBMPs) for TRE. Moreover, the results suggest that CBMPs are well-tolerated in the short term. The limitations mean causation cannot be determined in this open-label, case series.

Psilocybin is a psychoactive drug found in a variety of mushroom species around the world. It induces an altered state of consciousness that has been used in ceremonial settings since antiquity. It is now known beyond doubt that the psychoactive effect of psilocybin (more particularly, its active metabolite psilocin) is due to a functionally selective effect on type 2A serotonin receptors found in the brain. Users of psilocybin reliably report visual misperceptions, mystical experiences, and heightened emotions that can range from elation and euphoria to (less frequently) panic and paranoia. Psilocybin is often legally designated as a drug with high potential for abuse, dependence, and harm. This is not supported by scientific evidence. Early phase clinical trials with psilocybin given in a comfortable, medically controlled setting suggest that, in combination with psychological support from trained therapists, it may have a clinically useful therapeutic effect in a variety of mental health problems, ranging from addictions to depression, with the best evidence thus far in treatment resistant depression. Meanwhile, societal narratives of hype and hyperbole around psilocybin are reminiscent of events in the 1960s that ultimately led to criminalization of nonmedical use. The results of later phase clinical trials of psilocybin therapy are awaited. Until then, we remain in a position of equipoise.

Objectives Anxiety disorders are one of the most common reasons for seeking treatment with cannabis-based medicinal products (CBMPs). Current pharmacological treatments are variable in efficacy and the endocannabinoid system has been identified as a potential therapeutic target. This study aims to detail the changes in health-related quality-of-life (HRQoL) and clinical safety following CBMP therapy for generalized anxiety disorder. Methods A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in patient-reported outcome measures (the General Anxiety Disorder Scale (GAD-7), EQ-5D-5L (a measure of health-related quality of life), and Sleep Quality Scale (SQS)) at 1, 3 and 6 months. Statistical significance was defined as p

Background:Psilocybin, a psychoactive serotonin receptor partial agonist, has been reported to acutely reduce clinical symptoms of depressive disorders. Psilocybin’s effects on cognitive function have not been widely or systematically studied.Aim:The aim of this study was to explore the safety of simultaneous administration of psilocybin to healthy participants in the largest randomised controlled trial of psilocybin to date. Primary and secondary endpoints assessed the short- and longer-term change in cognitive functioning, as assessed by a Cambridge Neuropsychological Test Automated Battery (CANTAB) Panel, and emotional processing scales. Safety was assessed via endpoints which included cognitive function, assessed by CANTAB global composite score, and treatment-emergent adverse event (TEAE) monitoring.Methods:In this phase 1, randomised, double-blind, placebo-controlled study, healthy participants ( n = 89; mean age 36.1 years; 41 females, 48 males) were randomised to receive a single oral dose of 10 or 25 mg psilocybin, or placebo, administered simultaneously to up to six participants, with one-to-one psychological support – each participant having an assigned, dedicated therapist available throughout the session.Results:In total, 511 TEAEs were reported, with a median duration of 1.0 day; 67% of all TEAEs started and resolved on the day of administration. There were no serious TEAEs, and none led to study withdrawal. There were no clinically relevant between-group differences in CANTAB global composite score, CANTAB cognitive domain scores, or emotional processing scale scores.Conclusions:These results indicate that 10 mg and 25 mg doses of psilocybin were generally well tolerated when given to up to six participants simultaneously and did not have any detrimental short- or long-term effects on cognitive functioning or emotional processing.Clinical Trial Registration:EudraCT ( https://www.clinicaltrialsregister.eu/ ) number: 2018-000978-30.

Objectives To explore pain-specific, general health-related quality of life (HRQoL), and safety outcomes of chronic pain patients prescribed cannabis-based medicinal products (CBMPs). Methods A case series was performed using patients with chronic pain from the UK Medical Cannabis Registry. Primary outcomes were changes in Brief Pain Inventory short-form (BPI), Short-form McGill Pain Questionnaire-2 (SF-MPQ-2), Visual Analogue Scale-Pain (VAS), General Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5L, at 1, 3, and 6 months from baseline. Statistical significance was defined at p-value

BACKGROUND: There is a paucity of high-quality data on patient outcomes and safety after initiating treatment with cannabis-based medicinal products (CBMPs). The aim of this study was to assess the clinical outcomes and safety of CBMPs by analyzing patient-reported outcome measures and adverse events across a broad spectrum of chronic conditions. RESEARCH DESIGN AND METHODS: This study analyzed patients enrolled in the UK Medical Cannabis Registry. Participants completed the EQ-5D-5L to assess health-related quality of life, Generalized Anxiety Disorder-7 (GAD-7) questionnaire to measure anxiety severity, and the Single-item Sleep Quality Scale (SQS) to rate sleep quality at baseline and follow-up after 1, 3, 6, and 12 months. RESULTS: A total of 2833 participants met inclusion criteria. The EQ-5D-5L index value, GAD-7, and SQS all improved at each follow-up (p 0.050). Adverse events were reported by 474 (16.73%) participants. CONCLUSIONS: This study suggests that CBMPs are associated with an improvement in health-related quality of life in UK patients with chronic diseases. Treatment was tolerated well by most participants, but adverse events were more common in female and cannabis-naïve patients.

The following study evaluated the clinical outcomes of patients enrolled in the UK Medical Cannabis Registry, who were treated with inhaled dried flower (Adven® EMT2, Curaleaf International, Guernsey), and sublingual/oral medium-chain triglyceride-based oils (Adven, Curaleaf International, Guernsey) for chronic pain. In this cohort study, the primary outcomes were changes in validated patient reported outcome measures (PROMs) at 1, 3, and 6 months compared to baseline, and adverse event analysis. Statistical significance was defined as p < 0.050. Three hundred and forty-eight (45.7%), 36 (4.7%), and 377 (49.5%) patients were treated with oils, dried flower, or both, respectively. Patients treated with oils or combination therapy recorded improvements within health-related quality of life, pain, and sleep-specific PROMs at 1, 3, and 6 months (p < 0.050). Patients treated with combination therapy recorded improvements in anxiety-specific PROMs at 1, 3, and 6 months (p < 0.050). 1,273 (167.3%) adverse events were recorded, with previously cannabis naïve users, ex-cannabis users, and females more likely to experience adverse events (p < 0.050). This study observed an association between initiation of CBMP treatment and improved outcomes for chronic pain patients. Prior cannabis use and gender were associated with adverse event incidence. Placebo-controlled trials are still necessary to establish the efficacy and safety of CBMPs for chronic pain.

INTRODUCTION: There is growing evidence on the efficacy of cannabis-based medicinal products (CBMPs) for chronic pain (CP). Due to the interaction between CP and anxiety, and the potential impact of CBMPs on both anxiety and CP, this article aimed to compare the outcomes of CP patients with and without co-morbid anxiety following CBMP treatment. METHODS: Participants were prospectively enrolled and categorized by baseline General Anxiety Disorder-7(GAD-7) scores, into 'no anxiety'(GAD-7 0.050). The anxiety cohort reported greater improvements in EQ-5D-5L index values, SQS and GAD-7(p

Although pre-clinical experiments associate cannabinoids with reduced depressive symptoms, there is a paucity of clinical evidence. This study aims to analyze the health-related quality of life changes and safety outcomes in patients prescribed cannabis-based medicinal products (CBMPs) for depression.A series of uncontrolled cases from the UK Medical Cannabis Registry were analyzed. The primary outcomes were changes from baseline in the Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), Sleep Quality Scale (SQS), and EQ-5D-5 L at 1, 3, and 6 months. Secondary outcomes included adverse events incidence.129 patients were identified for inclusion. Median PHQ-9 at baseline was 16.0 (IQR: 9.0-21.0). There were reductions in PHQ-9 at 1-month (median: 8.0; IQR: 4.0-14.0; p 0.001), 3-months (7.0; 2.3-12.8; p 0.001), and 6-months (7.0; 2.0-9.5; p 0.001). Improvements were also observed in GAD-7, SQS, and EQ-5D-5L Index Value at 1, 3, and 6 months (p 0.050). 153 (118.6%) adverse events were recorded by 14.0% (n = 18) of participants, 87% (n = 133) of which were mild or moderate.CBMP treatment was associated with reductions in depression severity at 1, 3, and 6 months. Limitations of the study design mean that a causal relationship cannot be proven. This analysis provides insights for further study within clinical trial settings.Depression is a highly prevalent mental health condition with approximately one in five people affected by at least one episode of depression in their lifetime. Two cardinal symptoms of depression are low mood and loss of interest. Since depression is such a debilitating condition, improving quality of life is an important part of treatment.Antidepressant medications are currently an important part of treating depression, but the variability in their effectiveness means that there is a need for alternative treatments. Medicinal cannabis, which contains certain chemicals from the cannabis plant, has received growing interest as a potential novel treatment for depression. Due to the lack of clinical studies on the use of medicinal cannabis to treat depression, this study aims to assess the effects of medicinal cannabis on quality of life in patients suffering from depression.The study included 129 patients treated with medicinal cannabis for depression at Sapphire Medical Clinics. The results showed that medicinal cannabis was associated with improvements in depression and anxiety symptoms, as well as health-related quality of life, and sleep quality after 1, 3, and 6 months of treatment. Although there were numerous adverse events in a small number of patients, most of these were mild or moderate. A major limitation is that this study cannot determine the extent to which medicinal cannabis is directly responsible for the improvements in depression symptoms that were observed. Future studies should focus on conducting clinical trials which can better evaluate the true treatment effects of medicinal cannabis for depression.

Cannabis-based medicinal products (CBMPs) have shown promising preclinical activity in inflammatory bowel disease. However, clinical trials have not demonstrated significant effects on active inflammation. This study aims to analyze changes in health-related quality of life (HRQoL) and adverse events in IBD patients prescribed CBMPs.A case series from the UK Medical Cannabis Registry was performed. Primary outcomes included changes from baseline in the Short Inflammatory Bowel Disease Questionnaire (SIBDQ), Generalized Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), and EQ-5D-5L Index score at 1 and 3 months. Statistical significance was defined using p0.050. Secondary outcomes included incidence of adverse events.Seventy-six patients with Crohn's disease (n=51; 67.11%) and ulcerative colitis (n=25; 32.89%) were included. The median baseline SIBDQ score improved at 1 and 3 months. EQ-5D-5L index values, GAD-7 and SQS also improved after 3 months (p0.050). Sixteen (21.05%) patients reported adverse events with the majority being classified as mild to moderate in severity. No life-threatening AEs were reported.Patients treated with CBMPs for refractory symptoms of Crohn's disease and ulcerative colitis demonstrated a short-term improvement in IBD-specific and general HRQoL. Prior cannabis consumers reported greater improvement compared to cannabis-naïve individuals.

Background The current paucity of clinical evidence limits the use of cannabis-based medicinal products (CBMPs) in post-traumatic stress disorder (PTSD). This study investigates health-related quality of life (HRQoL) changes and adverse events in patients prescribed CBMPs for PTSD. Methods A case-series of patients from the UK Medical Cannabis Registry was analyzed. HRQoL was assessed at 1-, 3-, and 6-months using validated patient reported outcome measures (PROMs). Adverse events were analyzed according to the Common Terminology Criteria for Adverse Events version 4.0. Statistical significance was defined as p < 0.050. Results Of 162 included patients, 88.89% (n = 144) were current/previous cannabis users. Median daily CBMP dosages were 5.00 (IQR: 0.00–70.00) mg of cannabidiol and 145.00 (IQR: 100.00–200.00) mg of Δ9-tetrahydrocannabinol. Significant improvements were observed in PTSD symptoms, sleep, and anxiety across all follow-up periods (p < 0.050). There were 220 (135.8%) adverse events reported by 33 patients (20.37%), with the majority graded mild or moderate in severity (n = 190, 117.28%). Insomnia and fatigue had the greatest incidence (n = 20, 12.35%). Conclusions Associated improvements in HRQoL were observed in patients who initiated CBMP therapy. Adverse events analysis suggests acceptability and safety up to 6 months. This study may inform randomized placebo-controlled trials, required to confirm causality and determine optimal dosing.

Background: Recreational lysergic acid diethylamide (LSD) use is growing in popularity amid increasing research interest on psychedelics and their possible therapeutic potential yet; the potent psychotropic effects of LSD may result in adverse reactions and behaviour. Aims: This study aimed to investigate the 12-month incidence and nature of LSD-related adverse experiences resulting in emergency medical treatment (EMT) seeking in an international sample of people reporting LSD use. Methods: We use data from the 2017 Global Drug Survey – a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. Results: Out of 10,293 past-year LSD users, 102 (1.0%) reported seeking EMT, with a per-event risk estimate of 0.2%. Younger age, comorbid mental health conditions and higher frequency of use were associated with increased risk of EMT seeking. The most common symptoms were psychological, including anxiety, panic and confusion, with the most common explanatory factors cited by respondents being poor ‘setting’ and ‘mindset’. Most responders reported feeling back to normal within 24 h, but 11 participants experienced persistent issues after 4 weeks. Conclusion: The results suggest that LSD is a relatively safe drug in recreational settings. Adverse reactions are typically short-lived, self-limiting and psychological in nature. Sub-optimal set and setting were commonly reported as suspected contributory factors. Within clinical settings, patient screening, preparatory sessions and supervision should reduce these acute risks considerably.

Introduction: There is a growing body of literature supporting the efficacy of cannabis-based medicinal products (CBMPs). Despite an increase in prescribing globally, there is a paucity of high-quality clinical data on the efficacy of CBMPs for many conditions. This study aims to detail the changes in health-related quality of life (HRQoL) and associated clinical safety in patients prescribed CBMPs for any clinical indication from the UK Medical Cannabis Registry (UKMCR). Methods: An uncontrolled prospective case series of the UKMCR was analyzed. Primary outcomes included change from baseline in patient-reported outcome measures collected across all patients (the Generalized Anxiety Disorder Scale [GAD-7], EQ-5D-5L, and Sleep Quality Scale [SQS]) at 1, 3, and 6 months. Secondary outcomes included the self-reported incidence and severity of adverse events. Statistical significance was defined as p

Introduction Palliative care aims to improve quality of life through optimal symptom control and pain management. Cannabis-based medicinal products (CBMPs) have a proven role in the treatment of chemotherapy-induced nausea and vomiting. However, there is a paucity of high-quality evidence with regards to the optimal therapeutic regimen, safety, and effectiveness of CBMPs in palliative care, as existing clinical trials are limited by methodological heterogeneity. The aim of this study is to summarise the outcomes of the initial subgroup of patients from the UK Medical Cannabis Registry who were prescribed CBMPs for a primary indication of palliative care, cancer pain and chemotherapy-induced nausea and vomiting, including effects on health-related quality of life and clinical safety. Methods A case series from the UK Medical Cannabis Registry of patients, who were receiving CBMPs for the indication of palliative care was undertaken. The primary outcome consisted of changes in patient-reported outcome measures including EQ-5D-5L, General Anxiety Disorder-7 (GAD-7), Single-Item Sleep Quality Scale (SQS), Pain Visual Analog Scale (VAS) and the Australia-Modified Karnofsky Performance Scale at 1 and 3 months compared to baseline. Secondary outcomes included the incidence and characteristics of adverse events. Statistical significance was defined by p-value Results Sixteen patients were included in the analysis, with a mean age of 63.25 years. Patients were predominantly prescribed CBMPs for cancer-related palliative care (n = 15, 94%). The median initial CBD and THC daily doses were 32.0 mg (Range: 20.0–384.0 mg) and 1.3 mg (Range: 1.0–16.0 mg) respectively. Improvements in patient reported health outcomes were observed according to SQS, EQ-5D-5L mobility, pain and discomfort, and anxiety and depression subdomains, EQ-5D-5L index, EQ-VAS and Pain VAS validated scales at both 1-month and 3-months, however, the changes were not statistically significant. Three adverse events (18.75%) were reported, all of which were either mild or moderate in severity. Conclusion This small study provides an exploratory analysis of the role of CBMPs in palliative care in the first cohort of patients since CBMPs legalisation in the UK. CBMPs were tolerated with few adverse events, all of which were mild or moderate and resolved spontaneously. Further long-term safety and efficacy studies involving larger cohorts are needed to establish CBMPs role in palliative care, including comparisons with standard treatments.

Weld residual stress plays an important role in the production and operating performance of ship structures. Various factors such as background noise, vibration, movement during ship construction, a layer of primer on the plate surface, and a layer of paint after ship construction bring challenges to measure weld residual stress in a shipyard. Three large test panels made of DH-36, High-strength low-alloy steel (HSLA), HSLA-65, and HSLA-80 steels were fabricated to examine the feasibility of using commercially available portable x-ray diffraction (XRD) equipment to measure residual stress in a shipyard environment. The measured results show that portable XRD equipment provided reliable measurements, with the shipyard environment effects, on the panels made of DH-36 and HSLA-65. On the other hand, the primer affected the accuracy of measured residual stress on the panel made of HSLA-80, but electropolishing could have been used to remove the primer to achieve a good measurement. 1. Introduction Welding is one of the most important manufacturing processes in shipbuilding and inevitably induces residual stress and distortion on ship structures. In addition, flame straightening, often used to remove distortion in the final stage of shipbuilding, can result in even higher residual stress because of higher constraints after ship structures are assembled. It is well known that residual stress affects the buckling strength, fatigue performance, corrosion resistance, and dimensional stability of ship structures. As shipbuilding has been increasingly using thinner and higher strength materials such as HSLA-80 and HSLA-100 to reduce weight and increase mobility, residual stress plays an even more important role in the operating performance of ship structures. Understanding the residual stress evolution from raw material to a completed ship during service is critical to improve the ship's performance. Multiple methods have been developed to measure residual stress which can be classified into three categories: nondestructive techniques, semidestructive techniques, and destructive techniques. The common nondestructive techniques include x-ray diffraction (XRD) (Gou et al. 2015), neutron diffraction (Kartal et al. 2006; Palkowski et al. 2013), magnetic method, ultrasonic methods (Bray & Junghans 1995), and impact-indentation method (Lin et al. 2005; Choi et al. 2010; Zhu et al. 2015). The semidestructive techniques include holedrilling and ring-core methods, and the destructive techniques include block removal, splitting, layering, and contour methods (Tebedge et al. 1973; Leggatt et al. 1996). The U.S. Nuclear Regulatory Commission and the Electric Power Research Institute organized an international round robin program to measure weld residual stress in pressurized water reactor primary cooling loop components containing dissimilar metal welds (Fredette et al. 2011; Rathbun et al. 2011). Neutron diffraction, deep-hole drilling, XRD, surface-hole drilling, ring-core method, and contour method were used to measure residual stress in this program. The measured results between different measurement techniques were compared and validated against each other. In addition, a round robin study in Europe was conducted to investigate the accuracy of the XRD method from March 2012 to December 2013 (GKN & DAkkS 2014). Thirty laboratories and companies determined the residual stresses in the surface of two reference samples. Statistical evaluation of all results found that the XRD method has a good measurement accuracy. The robust means are between 4.7 and 6.3 MPa and the robust deviations are between 3.1 and 4.0 MPa. These studies have greatly improved the residual stress measurement techniques.

Experiments employing monochromatic light have been used to investigate the role of longitudinal chromatic aberration (LCA) as possible signals for emmetropization for many years. LCA arising from the dispersion of light, causes differences in the focal length at different wavelengths and can impose defocus (wavelength defocus). Short-wavelength light focuses with a shorter focal length than long-wavelength light and, as such, would be expected to produce a smaller, more hyperopic eye. Emmetropization can respond to wavelength defocus since animals reared in monochromatic light adjust their refractive state relative to that measured in white light. In many species, animals reared in monochromatic light respond as predicted by wavelength defocus, becoming more hyperopic in blue light and more myopic in red light. However, tree shrews and rhesus monkey become more hyperopic in red light, and while tree shrews initially become more hyperopic in blue light, they later become more myopic. This review examines the experiments performed in monochromatic light and highlights the potential differences in protocols affecting the results, including experiment duration, circadian rhythm stimulation, light intensity, bandwidth, humoral factors and temporal sensitivity.

Aircraft tie-downs have been widely used to secure airplanes, helicopters, and other transportation vehicles to a ship's deck. A multi-pass welding process is typically used for integrating tie-downs to the deck plate to develop the required strength at the joint. During and after welding, the surrounding deck material around the tie-downs must deform elastically to preserve dimensional continuity, creating residual stresses. Weld-induced residual stress is a major concern because the tie-downs are subject to cyclic, dynamic loading which could induce cracking and directly impact the fatigue life of the deck plate structures during services. To select an optimized welding sequence that minimizes weld-induced residual stress in the welded joint, an integrated computational materials engineering approach was used to evaluate the effect of welding sequences on residual stress distributions. Various deck materials (including ABS Grade DH36 and HSLA-100 steel alloys) and welding sequences were investigated to identify the optimized welding sequence which reduced radial residual stress distribution, resulting in lower final deck plate distortion. 1. Introduction Like many heavy industries, shipbuilding has a need for developing lightweight, high-strength, durable structures to improve payload capacity and mission performance, and reduce total ownership costs. The engineering design criteria and the thin-steel alloy material advancement developed to meet these requirements has outpaced the improvement of many manufacturing processes, necessitating a greater understanding of the influence of material properties on producibility issues during construction that could impact the performance of ship structures at sea. Residual stresses are "locked-in" stresses that develop in materials and structures because of welding or material handling processes during manufacturing that are independent of the presence of any external loads. Typical residual stress-induced buckling distortions in ship structures are developed as an elastic response to any incompatible local plastic strains that exist in the material after welding (Huang et al. 2003, 2004).

Psilocybin has a long history of non-medical use and some seem to infer from this that it has therapeutic utility. Early phase clinical trials with psilocybin are encouraging, but suggest only that larger, multicentre trials are required. These are ongoing but will take many years to complete. Meanwhile, retreat centers offering paid experiences with psilocybin truffles have opened in some countries, often using early phase clinical trial data as a basis for bold, public facing claims. This seems unwise. Early phase trials are not designed for their results to be generalized outside the setting they were undertaken in. To do so risks being misleading. Providing what may be seen as an unregulated drug intervention as a paid service is difficult to reconcile with long-held ethical principles underpinning human research and treatment development that were laid down by the 1947 Nuremberg Code and the 1962 Kefauver Harris Amendments. By using psilocybin before it has been properly tested, retreat centers may be undermining their own credibility and the credibility of the wider field.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown.We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48 % male) derived from 15 distinct MRI scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers – the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Recent research findings have strongly suggested that sport-related concussion (SRC) increases risk for subsequent injury of any type, as well as a potential for long-term adverse effects on neurological and psychological well-being. The primary purpose of this study was to explore the reliability and discriminatory power of clinical testing procedures for detecting persisting effects of SRC. We used a cross-sectional study design to assess both self-reported symptoms commonly associated with post-concussion syndrome, and the effects of mental or physical activity on metrics derived from a smartphone app designed to test perceptual-motor responses. Among 30 physically active college students, 15 participants reported a SRC occurrence prior to testing ( M time-since-injury = 4.0 years, SD = 3.1, range = 5 months to 11 years). We found good test-retest reliability for key metrics derived from the smartphone app (ICC ≥ .70); and the internal consistency for the Overall Wellness Index (OWI) for 10 categories of 82 post-concussion symptoms was ideal (Cronbach’s α ≥ .80). Moderate intensity treadmill running demonstrated the strongest differential effect on perceptual-motor responses between participants with a history of SRC (HxSRC) and those with no such history (No SRC), which was best represented by the speed-accuracy trade-off quantified by the inverse efficiency index (IEI: group X trial interaction p = .055). Self-reported OWI symptoms ≥4 and post-physical activity IEI ≥ 568 ms provided the strongest discrimination between HxSRC and NoSRC participants (≥1 versus 0: OR = 9.75). Our findings suggest that persisting effects from a remote SRC occurrence can be detected by easily administered screening procedures that have the potential to identify individual athletes who might derive benefit from interventions to restore their optimal function and well-being.

As a result of longitudinal chromatic aberration (LCA), longer wavelengths are blurred when shorter wavelengths are in focus, and vice versa. As a result, LCA affects the color and temporal aspects of the retinal image with hyperopic defocus. In this experiment, we investigated how the sensitivity to temporal color contrast affects emmetropization. Ten-day-old chicks were exposed for three days to sinusoidal color modulation. The modulation was either blue/yellow flicker (BY) (n = 57) or red/green flicker (RG) (n = 60) simulating hyperopic defocus with and without a blue light component. The color contrasts tested were 0.1, 0.2, 0.3, 0.4, 0.6, and 0.8 Michelson contrast. The mean illuminance of all stimuli was 680 lux. Temporal modulation was either of a high (10 Hz) or low (0.2 Hz) temporal frequency. To test the role of short- and double-cone stimulation, an additional condition silenced these cones in RG_0.4 (D-) and was compared with RG_0.4 (D+) (n = 14). Changes in ocular components and refractive error were measured using Lenstar and a photorefractometer. With high temporal frequency BY representing an in-focus condition for shorter-wavelengths, we found that high temporal frequency BY contrast was positively correlated with vitreous expansion (R2 = 0.87, p

A previous experiment showed that blue light (as a component of white light) protected against low temporal frequency dependent eye growth. This experiment investigated the role of temporal contrast. White leghorn chicks were exposed to white (with blue) or yellow (without blue) LED lighting modulated at either low (0.2 Hz) or high (10 Hz) temporal frequencies. Four cone contrast conditions were used: low (16%), medium (32%), medium-high (60%) and very-high (80%). Chicks were exposed to the lighting condition for 3 days (mean 680 lux). Exposure to high temporal frequencies, with very high temporal contrast, reduced eye growth, regardless of spectral content. However, at low temporal frequencies, eye growth was dependent on the illuminant. At lower temporal contrast levels, eye growth increased regardless of temporal or spectral characteristics. To conclude, very high temporal contrast, white light, provides a “stop” signal for eye growth that overrides temporal cues for growth that manifest in yellow light.

Purpose Longitudinal chromatic aberration can provide luminance and chromatic signals for emmetropization. A previous experiment examined the role of temporal sensitivity to luminance flicker in the emmetropization response. In the current experiment, we investigate the role of temporal sensitivity to color flicker. Methods Five-day-old chicks were exposed to sinusoidal color modulation of blue/yellow (N = 73) or red/green LEDs (N = 84) at 80% contrast for 3 days. The modulation frequencies used were as follows: 0, 0.2, 1, 2, 5, and 10 Hz. There were 5 to 16 chicks per condition. Mean illumination was 680 lux. Changes in ocular components were measured using Lenstar, and refraction was measured with a Hartinger refractometer. Results Eyes grew less when exposed to high temporal frequencies and more at low temporal frequencies. With blue/yellow modulation, the temporal variation was small; eyes grew 268 ± 15 μm at 0 Hz and 224 ± 12 μm at 10 Hz, representing a 16.4% growth reduction. With red/green modulation, eyes grew 336 ± 31 μm at 0 Hz and 218 ± 20 μm at 10 Hz, representing a 35% growth reduction. Choroidal and anterior chamber changes compensated for eye growth, reducing refractive effects; blue/yellow refraction changes ranged from -0.63 to 1.04 diopters. Conclusions At high temporal frequencies, color is not a factor, but at low temporal frequencies, red/green modulation produced maximal growth. The pattern of changes observed in each ocular component with changes in the temporal frequency and/or the color of the stimulus was consistent with the idea that the natural sunlight spectrum may be optimal for emmetropization.

Chicks respond to two signals from longitudinal chromatic aberration (LCA): a wavelength defocus signal and a chromatic signal. Wavelength defocus predicts reduced axial eye growth in monochromatic short-wavelength light, compared to monochromatic long-wavelength light. Wavelength defocus may also influence growth in broadband light. In contrast, a chromatic signal predicts increased growth when short-wavelength contrast > long-wavelength contrast, but only when light is broadband. We aimed to investigate the influence of blue light, temporal frequency and contrast on these signals under broadband conditions. Starting at 12 to 13 days-old, 587 chicks were exposed to the experimental illumination conditions for three days for 8h/day and spent the remainder of their day in the dark. The stimuli were flickering lights, with a temporal frequency of 0.2 or 10 Hz, low (30%) or high contrast (80%), and a variety of ratios of cone contrast simulating the effects of defocus with LCA. There were two color conditions, with blue contrast (bPlus) and without (bMinus). Stimuli in the “bPlus” condition varied the amounts of long- (L-), middle- (M-) and double- (D-) cone contrast, relative to short- (S-) and ultraviolet (UV-) cone contrast, to simulate defocus. Stimuli in the “bMinus” condition only varied the relative modulations of the L+D vs. M cones. In all cases, the average of the stimuli was white, with an illuminance of 777 lux, with cone contrast created through temporal modulation. A Lenstar LS 900 and a Hartinger refractometer were used to measure ocular components and refraction. Wavelength defocus signals with relatively high S-cone contrast resulted in reduced axial growth, and more hyperopic refractions, under low-frequency conditions (p = 0.002), in response to the myopic defocus of blue light. Chromatic signals with relatively high S-cone contrast resulted in increased axial growth and more myopic refractions, under high frequency, low contrast, conditions (p < 0.001). We conclude that the chromatic signals from LCA are dependent on the temporal frequency, phase, and relative contrast of S-cone temporal modulation, and recommend broadband spectral and temporal environments, such as the outdoor environment, to optimize the signals-for-defocus in chick.

Stroboscopic luminance flicker has been found to prevent the increase in eye growth normally associated with form deprivation through the release of retinal dopamine. In this study, we sought to investigate whether dopamine plays a role in the decreased growth observed with 2 Hz sine-wave luminance flicker and increased growth with color flicker. Starting 5–7 days after hatching, chicks were exposed to 2 Hz sinusoidally modulated illumination (Mean: 680 lux) for 4 days and were otherwise in the dark. Chicks were exposed to color-modulated red and green (RG) light, to luminance modulated RGB components (LUM), or to a no-flicker (NF) control. Chicks received daily 10 μL intravitreal injections of apomorphine, spiperone, or saline. Fellow eyes received no injection. Spiperone injections prevented the decrease in eye growth typically seen with LUM flicker, with a relative increase in eye length, but no other significant effects compared with saline controls. Apomorphine injections prevented the increase in eye growth typically seen with RG flicker, with a relative decrease in eye length compared to saline controls. These results indicate a role for the activation of D2-receptor types in the inhibition of eye growth in response to luminance flicker, and a lack of dopamine receptor activation associated with the increase in eye growth with color flicker.

In broadband light, longitudinal chromatic aberration (LCA) provides emmetropization signals from both wavelength defocus and the resulting chromatic cues. Indoor illuminants vary in their spectral output, potentially limiting the signals from LCA. Our aim is to investigate the effect that artificial illuminants with different spectral outputs have on chick emmetropization with and without low temporal frequency modulation. In Experiment 1, two-week-old chicks were exposed to 0.2 Hz, square-wave luminance modulation for 3 days. There were 4 spectral conditions: LED strips that simulated General Electric (GE) LED "Soft" (n = 13), GE LED "Daylight" (n = 12), a novel "Equal" condition (n = 12), and a novel "High S" condition (n = 10). These conditions were all tested at a mean level of 985 lux. In Experiment 2, the effect of intensity on the "Equal" condition was tested at two other light levels (70 lux: n = 10; 680 lux: n = 7). In Experiment 3, the effect of temporal modulation on the "Equal" condition was tested by comparing the 0.2 Hz condition with 0 Hz (steady). Significant differences were found in axial growth across lighting conditions. At 985 lux, birds exposed to the "Equal" condition showed a greater reduction in axial growth (both p 0.01) and a greater hyperopic shift compared to "Soft" and "Daylight" (both p 0.01). The "High S" birds experienced more axial growth compared to "Equal" (p 0.01) but less than in "Soft" and "Daylight" (p 0.01). Axial changes in "Equal" were only observed at 985 lux with 0.2 Hz temporal modulation, and not with lower light levels or steady light. We conclude that axial growth and refraction were dependent on the lighting condition in a manner predicted by wavelength defocus signals arising from LCA.

Purpose Longitudinal chromatic aberration (LCA) is a color signal available to the emmetropization process that causes greater myopic defocus of short wavelengths than long wavelengths. We measured individual differences in chromatic sensitivity to explore the role LCA may play in the development of refractive error. Methods Forty-four observers were tested psychophysically after passing color screening tests and a questionnaire for visual defects. Refraction was measured and only subjects with myopia or hyperopia without severe astigmatism participated. Psychophysical detection thresholds for 3 cyc/deg achromatic, L-, M-, and S-cone-isolating Gabor patches and low-frequency S-cone increment (S+) and decrement (S-) blobs were measured. Parametric Pearson correlations for refractive error versus threshold were calculated and nonparametric bootstrap 95% percentage confidence intervals (BCIs) for r were computed. Results S-cone Gabor detection thresholds were higher than achromatic, L-, and M-cone Gabors. S-cone Gabor thresholds were higher than either S+ or S- blobs. These results are consistent with studies using smaller samples of practiced observers. None of the thresholds for the Gabor stimuli were correlated with refractive error (RE). A negative correlation with RE was observed for both S+ (r = -0.28; P = 0.06; BCI: r = -0.5, -0.04) and S- (r = -0.23; P = 0.13; BCI = -0.46, 0.01) blobs, although this relationship did not reach conventional statistical significance. Conclusions Thresholds for S+ and S- stimuli were negatively related to RE, indicating that myopes may have reduced sensitivity to low spatial frequency S-cone stimuli. This reduced S-cone sensitivity might have played a role in their failure to emmetropize normally.

Introduction Black individuals continue to be underrepresented in clinical trials despite efforts by the National Institutes of Health and the Federal Drug Administration to increase their enrollment. Health care providers play a critical role in the recruitment of patients into clinical trials, as they have established relationships and are uniquely positioned to make referrals for participation. While prior initiatives have focused on training black physicians to conduct clinical research, we sought to determine the potential of utilizing a professional organization as a resource to identify established investigators to champion recruitment of underrepresented racial and ethnic populations. The Association of Black Cardiologists (ABC) is a non-profit organization with a mission to eliminate racial and ethnic disparities in cardiovascular disease and may provide a conduit for recruiting investigators. The purpose of this study was to examine the feasibility of using the ABC membership to identify investigators with an established track record in clinical trials. Methods/Results Utilizing a roster of ABC members, we searched Scopus to quantify ABC member publications from 1999 to 2015 and identify members who have been active in clinical trials. Within the membership of 2037 individuals, we identified 794 with peer-reviewed publications, and 109 who co-authored manuscripts involving randomized clinical trials. The manuscripts largely focused on hypertension and heart failure, conditions that have a disproportionately greater affect on black individuals. Conclusion Members of the ABC have varied amounts of research productivity. We identified a group of experienced investigators to engage in efforts aimed at recruiting/enrolling underrepresented racial and ethnic populations in clinical trials of cardiovascular disease.

Welding, as a major manufacturing process in shipbuilding, induces residual stress and distortion that affects buckling strength, fatigue performance, corrosion resistance, and dimensional stability of ship structures. Understanding residual stress in ship structures is required in engineering design to ensure structural strength and safety and is essential in dimensional accuracy for distortion control during fabrication. However, measuring residual stress in ship structures presents unique challenges, such as structure complexity, surface primer, and a non-friendly measurement environment. Fortunately, portable X-ray diffraction equipment has been successfully developed and proven accurate in other industries to measure residual stress. This study is to evaluate the feasibility of measuring residual stress in a shipyard environment in terms of accuracy and adaptability. Typical welded joints (butt joint and T-joint) were selected for evaluation instead of evaluating complicated ship structures. The welded joints were fabricated using common shipyard welding procedures. This makes the evaluation easier since weld residual stress distributions and magnitudes on these joints are well understood. In addition, the hole-drilling method was also used to validate the X-ray diffraction results. Measured results show that X-ray diffraction can penetrate the pre-construction surface primer used in shipbuilding to directly measure residual stress of the metal surface, without the need to remove the surface primer. The residual stress data measured by X-ray diffraction agreed with the data obtained by the hole-drilling method. In addition, the residual stress trend measured by X-ray diffraction agreed with the theoretical residual-stress distributions. This study concluded that a portable X-ray diffraction is a potential technology for residual stress measurement in a shipyard.

Purpose At birth most, but not all eyes, are hyperopic. Over the course of the first few years of life the refraction gradually becomes close to zero through a process called emmetropisation. This process is not thought to require accommodation, though a lag of accommodation has been implicated in myopia development, suggesting that the accuracy of accommodation is an important factor. This review will cover research on accommodation and emmetropisation that relates to the ability of the eye to use colour and luminance cues to guide the responses. Recent Findings There are three ways in which changes in luminance and colour contrast could provide cues: (1) The eye could maximize luminance contrast. Monochromatic light experiments have shown that the human eye can accommodate and animal eyes can emmetropise using changes in luminance contrast alone. However, by reducing the effectiveness of luminance cues in monochromatic and white light by introducing astigmatism, or by reducing light intensity, investigators have revealed that the eye also uses colour cues in emmetropisation. (2) The eye could compare relative cone contrast to derive the sign of defocus information from colour cues. Experiments involving simulations of the retinal image with defocus have shown that relative cone contrast can provide colour cues for defocus in accommodation and emmetropisation. In the myopic simulation the contrast of the red component of a sinusoidal grating was higher than that of the green and blue component and this caused relaxation of accommodation and reduced eye growth. In the hyperopic simulation the contrast of the blue component was higher than that of the green and red components and this caused increased accommodation and increased eye growth. (3) The eye could compare the change in luminance and colour contrast as the eye changes focus. An experiment has shown that changes in colour or luminance contrast can provide cues for defocus in emmetropisation. When the eye is exposed to colour flicker the eye grows almost twice as much, and becomes more myopic, compared to when the eye is exposed to luminance flicker. Summary Neural responses of the luminance and colour mechanisms direct accommodation and emmetropisation mechanisms to different focal planes. Therefore, it is likely that the set point of refraction and accommodation is dependent on the sensitivity of the eye to changes in spatial and temporal, colour and luminance contrast.

Gastroesophageal reflux disease (GERD), abdominal pain of unknown origin, and constipation are thought to be causes for frequent medical visits during childhood. The aim of this study was to estimate the incidences, repeat presentation, clinical symptoms, and sociodemographic risk factors in children who medically presented for GERD, abdominal pain of unknown origin, and constipation from birth to 5 years.This was a population-based, retrospective birth cohort study of all children born to mothers residing in Rochester, Minnesota who remained in the area until at least age 5 (n = 5718). The medical records of all individuals were searched for relevant diagnostic billing codes for GERD, abdominal pain of unknown origin, and constipation, without another underlying diagnosis, and manually reviewed. Parental sociodemographic factors collected from birth certificate records on patients and matched controls were compared.The incidence for childhood (age,5 y) presentation of GERD, abdominal pain of unknown origin, and constipation was .9/1000 person-years, 4.5/1000 person-years, and 6.8/1000 person-years, respectively; there were no significant differences between boys and girls. Three or more medical visits by age 5 occurred in 11%, 19%, and 24% of children who were seen for abdominal pain of unknown origin, constipation, and GERD, respectively. Single parentage, maternal age (18 y), and maternal education (high school) were not associated with abdominal pain or constipation presentation.The incidences of presentation for GERD, abdominal pain of unknown origin, and constipation are among the highest for pediatric disorders, and a cause for repeated medical consultations.

Time spent outdoors is protective against myopia. The outdoors allows exposure to short-wavelength (blue light) rich sunlight, while indoor illuminants can be deficient at short-wavelengths. In the current experiment, we investigate the role of blue light, and temporal sensitivity, in the emmetropization response.Five-day-old chicks were exposed to sinusoidal luminance modulation of white light (with blue; N = 82) or yellow light (without blue; N = 83) at 80% contrast, at one of six temporal frequencies: 0, 0.2, 1, 2, 5, 10 Hz daily for 3 days. Mean illumination was 680 lux. Changes in ocular components and corneal curvature were measured.Refraction, eye length, and choroidal changes were dependent on the presence of blue light (P0.03, all) and on temporal frequency (P0.03, all). In the presence of blue light, refraction did not change across frequencies (mean change -0.24 [diopters] D), while in the absence of blue light, we observed a hyperopic shift (1 D) at high frequencies, and a myopic shift (-0.6 D) at low frequencies. With blue light there was little difference in eye growth across frequencies (77 μm), while in the absence of blue light, eyes grew more at low temporal frequencies and less at high temporal frequencies (10 vs. 0.2 Hz: 145 μm; P0.003). Overall, neonatal astigmatism was reduced with blue light.Illuminants rich in blue light can protect against myopic eye growth when the eye is exposed to slow changes in luminance contrast as might occur with near work.

This study analyzed the luminance and color emmetropization response in chicks treated with the nonselective parasympathetic antagonist atropine and the sympathetic β-receptor blocker timolol.Chicks were binocularly exposed (8h/day) for 4days to one of three illumination conditions: 2Hz sinusoidal luminance flicker, 2Hz sinusoidal blue/yellow color flicker, or steady light (mean 680lux). Atropine experiments involved monocular daily injections of either 20μl of atropine (18nmol) or 20μl of phosphate-buffered saline. Timolol experiments involved monocular daily applications of 2 drops of 0.5% timolol or 2 drops of distilled H2O. Changes in the experimental eye were compared with those in the fellow eye after correction for the effects of saline/water treatments.Atropine caused a reduction in axial length with both luminance flicker (−0.078±0.021mm) and color flicker (−0.054±0.017mm), and a reduction in vitreous chamber depth with luminance flicker (−0.095±0.023mm), evoking a hyperopic shift in refraction (3.40±1.77D). Timolol produced an increase in axial length with luminance flicker (0.045±0.030mm) and a myopic shift in refraction (−4.07±0.92D), while color flicker caused a significant decrease in axial length (−0.046±0.017mm) that was associated with choroidal thinning (−0.046±0.015mm).The opposing effects on growth and refraction seen with atropine and timolol suggest a balancing mechanism between the parasympathetic and β-receptor mediated sympathetic system through stimulation of the retina with luminance and color contrast.

Summary Background The effects of tegaserod on gastric accommodation and postprandial satiety remain unclear. Aim To compare the effects of tegaserod 6 mg twice daily vs. placebo on gastric volumes, postprandial symptoms, gastric emptying, small bowel transit and the surface electrogastrogram in female and male healthy volunteers. Methods Randomized, double-blind, placebo-controlled study evaluated gastric function before and after 7 days of tegaserod 6 mg twice daily (n = 21) vs. placebo (n = 20) in healthy volunteers. Validated methods were used to study gastric emptying, myoelectrical activity, volumes and satiation postnutrient challenge. Results There were no significant effects of tegaserod on the primary endpoints assessing gastric function: emptying of solids or liquids, total gastric volumes or myoelectrical activity. Maximum tolerated volume and aggregate symptom score with nutrient challenge on placebo were 1035 mL (±44) and 130 (±15) vs. 989 mL (±43) and 117 (±15) during tegaserod, respectively (all P = N.S.). Postprandial change in proximal gastric volume by single photon emission-computed tomography was decreased in females on tegaserod (246 ± 30) vs. placebo (358 ± 32) (P = 0.015). Proximal fasting volumes in females were increased on tegaserod (126 ± 12) vs. placebo (92 ± 13) (P = 0.066). Conclusions While tegaserod decreased proximal gastric volume change after a meal, it does not appear to have significant effects on gastric motor and sensory function in healthy individuals. Further studies are required in patients with disturbances of gastric motor and sensory function.

Background: Antidepressants are widely used to treat functional gastrointestinal disorders but their effect on postprandial symptoms remains unstudied. We hypothesized that desipramine and escitalopram would enhance the maximum tolerated volume of nutrient ingested and decrease postprandial symptoms. Methods: Healthy participants (n = 45) all underwent an assessment of symptoms, anxiety and depression, and a standard nutrient drink test (Ensure). Participants were randomized to 11 days of desipramine (50 mg once daily), escitalopram (10 mg once daily) or identical placebo. Results: The maximum tolerated gastric volumes were not significantly different on day 11 for desipramine (1,136 ± 478 ml, mean ± SD), escitalopram (1,198 ± 422 ml) and placebo (1,231 ± 318 ml). A univariate analysis indicated significant treatment group effects on total symptom scores (p = 0.049), but after adjusting for age, gender, BMI and baseline scores, treatment effects were no longer significant (p = 0.15). Conclusions: While this study does not rule out a beneficial effect of tricyclics or selective serotonin reuptake inhibitors in functional dyspepsia, neither desipramine nor escitalopram significantly altered the nutrient volume ingested or symptoms induced by the nutrient drink test in healthy volunteers.