Interactions Between the Basolateral Amygdala and Ventral Striatum During Probabilistic Learning in Children and Associations with Individual Differences in Free Cortisol

Stress can drastically alter the behavioural and functional correlates of feedback learning; however, the functional correlates of these effects are poorly understood, particularly in children. In the present study, typically developing children between the ages of 9- and 11-years-old completed a probabilistic learning task with both appetitive and aversive outcomes in a magnetic resonance imaging scanner. Anticipatory stress to the experimental environment was measured via salivary cortisol at baseline and prior to completion of the task. Although baseline and pre-MRI cortisol values were not reliably different at the group level, subsequent analyses revealed that the basolateral amygdala was less responsive to positive feedback in children with higher pre-MRI cortisol levels. Furthermore, individual differences in feedback-related basolateral amygdala activity were positively associated with differences in striatal activity. Thus, the basolateral amygdala may be particularly sensitive to individual differences in active cortisol levels, and may also modulate striatal feedback sensitivity

Intravenous versus subcutaneous drug administration. Which do patients prefer? A systematic review

BACKGROUND: Intravenous (IV) drug delivery is commonly used for its rapid administration and immediate drug effect. Most studies compare IV to subcutaneous (SC) delivery in terms of safety and efficacy, but little is known about what patients prefer. METHODS: A systematic review was conducted by searching seven electronic databases for articles published up to February 2014. Included studies were randomized controlled trials (RCTs) and/or crossover designs investigating patient preference for SC versus IV administration. The risk of bias in the RCTs was determined using the Cochrane Collaboration tool. Reviewers independently extracted data and assessed the risk of bias. Any discrepancies were resolved by consensus. RESULTS: The search identified 115 publications, but few (6/115) met the inclusion criteria. Patient populations and drugs investigated were diverse. Four of six studies demonstrated a clear patient preference for SC administration. Main factors associated with SC preference were time saving and the ability to have treatment at home. Only three studies used study-specific instruments to measure preference. CONCLUSIONS: Results suggest that patients prefer SC over IV delivery. Patient preference has clearly been neglected in clinical research, but it is important in medical decision making when choosing treatment methods as it has implications for adherence and quality of life. If the safety and efficacy of both administration routes are equivalent, then the most important factor should be patient preference as this will ensure optimal treatment adherence and ultimately improve patient experience or satisfaction. Future drug efficacy and safety studies should include contemporaneous, actual patient preference where possible, utilizing appropriate measures

Information needs of patients with cancer: results from a large study in UK cancer centres

As part of a multi-centred study evaluating a communication skills training model for clinicians, we collected information preferences using an adaptation of Cassileth's Information Needs questionnaire from a heterogeneous sample of 2331 patients. Results showed that 87% (2027) wanted all possible information, both good and bad news and 98% (2203) preferred to know whether or not their illness was cancer. Cross tabulation of responses revealed no significant differences in information preferences for tumour site or treatment aims but did show an effect of age and sex. The few 58/440 (13.2%) patients who stated that in general they preferred to leave disclosure of details up to the doctor, tended to be older patients more than 70 years of age (chi square = 26.01, df = 2, P< 0.0001), although paradoxically they still wanted to know certain specific details. In comparison to men women preferred to know the specific name of the illness (chi square = 4.9, df = 1, P< 0.02) and what were all the possible treatments (chi square = 8.26, df = 1, P< 0.004). The results from this very large sample provide conclusive evidence that the vast majority of patients with cancer want a great deal of specific information concerning their illness and treatment. Failure to disclose such information on the grounds that significant numbers of patients prefer not to know is untenable. © 2001 Cancer Research Campaign http://www.bjcancer.co

Influence of a 12.8-km military load carriage activity on lower limb gait mechanics and muscle activity

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this record.The high stress fracture occurrence in military populations has been associated with frequent load carriage activities. This study aimed to assess the influence of load carriage and of completing a load carriage training activity on gait characteristics. Thirty-two Royal Marine recruits completed a 12.8-km load carriage activity as part of their military training. Data were collected during walking in military boots, pre and post-activity, with and without the additional load (35.5 kg). Ground contact time, lower limb sagittal plane kinematics and kinetics, and electromyographic variables were obtained for each condition. When carrying load, there was increased ground contact time, increased joint flexion and joint moments, and increased plantar flexor and knee extensor muscle activity. Post-activity, there were no changes to kinematic variables, knee extensor moments were reduced, and there was evidence of plantar flexor muscle fatigue. The observed gait changes may be associated with stress fracture development. Practitioner Summary: This study identified gait changes due to load carriage and after a military load carriage training activity. Such activities are associated with lower limb stress fractures. A pre-post study design was used. Gait mechanics changed to a greater extent when carrying load, than after completion of the activity when assessed without load.This work was part-funded by the Institute of Naval Medicine

Noninvasive Evaluation of Portal Hypertension: Emerging Tools and Techniques

Portal hypertension is the main cause of complications in patients with cirrhosis. However, evaluating the development and progression of portal hypertension represents a challenge for clinicians. There has been considerable focus on the potential role of noninvasive markers of portal hypertension that could be used to stratify patients with respect to the stage of portal hypertension and to monitor disease progression or treatment response in a longitudinal manner without having to undertake repeated invasive assessment. The pathogenesis of portal hypertension is increasingly understood and emerging knowledge of the vascular processes that underpin portal hypertension has paved the way for exploring novel biomarkers of vascular injury, angiogenesis, and endothelial dysfunction. In this paper we focus on the pathogenesis of portal hypertension and potential non-invasive biomarkers with particular emphasis on serum analytes

Altered forefoot function following a military training activity

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordBackground Injury rates are high in populations that regularly undertake weight-bearing physical activity, particularly military populations. Military training activities, that often include load carriage, have been associated with lower limb injury occurrence, specifically stress fractures. Research question Recent work identified plantar loading variables as risk factors for lower limb stress fractures in Royal Marines recruits that were assessed during barefoot running. This study aimed to quantify how those plantar loading variables changed in Royal Marines recruits following a prolonged military load carriage activity, to further understand potential mechanisms for lower limb stress fractures. Methods Bilateral, synchronised plantar pressure and lower limb kinematic data were recorded during barefoot running at 3.6 m s-1 (±5%) pre- and post- a 12.8-km training activity (∼150 min). The training activity was completed with an average speed typical of walking (1.4 m.s-1), and 35.5 kg of additional load was carried throughout. Data were collected from 32 male Royal Marines recruits who completed the training activity in week-21 of the 32-week training programme. Plantar pressure variables and ankle dorsiflexion were compared between pre- and post-activity. Results Post-activity there was reduced loading under the forefoot and increased loading under the rearfoot and midfoot. There was no change in dorsiflexion touchdown angle, but an increase in peak dorsiflexion and range of motion post-activity. Significance The increased rearfoot loading, reduced forefoot loading and increased ankle dorsiflexion following a prolonged military load carriage activity suggest a reduced transfer of loading from the rearfoot to the forefoot during stance, which may have implications for the development of stress fractures, particularly of the metatarsals.Institute of Naval Medicin

Implications of subcutaneous or intravenous delivery of trastuzumab: further insight from patient interviews in the PrefHer study

BACKGROUND: The 2 Cohort randomised PrefHer trial examined the preferences of HER2+ve primary breast cancer patients for intravenous (IV) or subcutaneous (SC) delivery of trastuzumab via a Single Injectable Device (SID) or hand-held syringe (HHS). The novel approach and design of the study permitted an in-depth exploration of patients' experiences, the impact that different modes of delivery had on patients' well-being and implications for future management. METHODS: The preferences, experiences and general comments of patients in the PrefHer study were collected via specific semi-structured interview schedules. Exploratory analyses of data were conducted using standard methodology. The final question invited patients to make further comments, which were divided into 9 thematic categories - future delivery, compliments, time/convenience, practical considerations, pain/discomfort, study design, side-effects, psychological impact, and perceived efficacy. RESULTS: 267/467 (57%) patients made 396 additional comments, 7 were neutral, 305 positive and 86 negative. The three top categories generating the largest number of comments were compliments and gratitude about staff and being part of PrefHer (75/396; 19%), the potential future delivery of SC trastuzumab (73/396; 18%), and practical considerations about SC administration (60/396; 15%). CONCLUSIONS: Eliciting patient preferences about routes of administration of drugs via comprehensive interviews within a randomised cross-over trial yielded rich and important information. The few negative comments made demonstrated a need for proper staff training in SC administration Patients were grateful to have been part of the trial, and would have liked to continue with SC delivery. The possibility of home administration in the future also seemed acceptable. EUDRACT NUMBER: 2010-024099-25

A data-driven approach to decode metabolic dysfunction-associated steatotic liver disease

Metabolic dysfunction-associated steatotic liver disease (MASLD), defined by the presence of liver steatosis together with at least one out of five cardiometabolic factors, is the most common cause of chronic liver disease worldwide, affecting around one in three people. Yet the clinical presentation of MASLD and the risk of progression to cirrhosis and adverse clinical outcomes is highly variable. It therefore represents both a global public health threat and a precision medicine challenge. The use of artificial intelligence (AI) is being investigated in MASLD to develop reproducible, quantitative, and automated methods to enhance patient stratification and to discover new biomarkers and therapeutic targets in MASLD. This review details the different applications of AI and machine learning algorithms in MASLD, particularly in the context of analyzing electronic health record, digital pathology, and imaging data. Additionally, it also describes how specific MASLD consortia are leveraging multimodal data sources to spark research breakthroughs in the field. Using a new national level ‘data commons’ (SteatoSITE) as an exemplar, the opportunities as well as the technical challenges of large-scale databases in MASLD research are highlighted

Communication skills training in oncology: a position paper based on a consensus meeting among European experts in 2009

Background: Communication in cancer care has become a major topic of interest. Since there is evidence that ineffective communication affects both patients and oncology clinicians (physicians and nurses), so-called communication skills trainings (CSTs) have been developed over the last decade. While these trainings have been demonstrated to be effective, there is an important heterogeneity with regard to implementation and with regard to evidence of different aspects of CST. Methods: In order to review and discuss the scientific literature on CST in oncology and to formulate recommendations, the Swiss Cancer League has organised a consensus meeting with European opinion leaders and experts in the field of CST, as well as oncology clinicians, representatives of oncology societies and patient organisations. On the basis of a systematic review and a meta-analysis, recommendations have been developed and agreed upon. Results: Recommendations address (i) the setting, objectives and participants of CST, (ii) its content and pedagogic tools, (iii) organisational aspects, (iv) outcome and (v) future directions and research. Conclusion: This consensus meeting, on the basis of European expert opinions and a systematic review and meta-analysis, defines key elements for the current provision and future development and evaluation of CST in oncolog