The law of love

Thesis (M.A.)--Boston Universit

Ultrasound Based Quantitative Motion Measurement using Speckle Size Estimation

An ultrasound system determines the relative movement in a first direction (F1) of first matter, such as blood flow, and second matter, such as an artery wall, in a subject under study (S). A beam (B1) of ultrasound waves defining a plurality of beam positions (BP1 and BP2) and beam axes (A1 and A2) are moved in scan direction having components parallel to direction F1. First and second blocks of data representing the first and second matter, respectively, are generated. A processor (20) performs an estimation of speckle size on first data to obtain a first result, and performs analysis of the second block of data to obtain a second result. The two results are analyzed to obtain a measure of the relative movement of the first and second matter

The development and evaluation of a computerised decision support system for primary care based upon 'patient profile decision analysis'

Objective To develop and evaluate in primary care a computerised decision support system for the management of stroke patients based upon 'patient profile decision analysis'. Design The decision support system incorporated the findings of 960 Markov models examining the decision to prescribe aspirin in the secondary prevention of stroke. The models reflected each combination of nine risk factors that determined a patient's profile. The evaluation comprised a qualitative interview and a questionnaire administered before and after the general practitioners (GPs) were given access to the support system. Setting Primary care. Participants 15 GPs from the West Midlands. Main outcome measures Decision certainty scoring of hypothetical patient vignettes. Qualitative perceptions of the applicability and acceptability of the system for primary care. Results After using the system, GPs were more certain of their decision making and made decisions more in line with national guidelines. Quantitative results further suggested that the system made decision making easier, improved feelings of being supported, improved the quality of decision making and increased satisfaction. Qualitative themes included that GPs thought the system could clarify their own decision making and improve GP_patient dialogue. Conclusions The feasibility of individualised decision analysis for general practice has been questioned. Patient profile decision analysis, however, may be a valuable means of harnessing some of the advantages of the methodology to produce more patient-specific guidelines for primary care

Identification of structural brain alterations in adolescents with depressive symptomatology

Introduction: Depressive symptoms can emerge as early as childhood and may lead to adverse situations in adulthood. Studies have examined structural brain alternations in individuals with depressive symptoms, but findings remain inconclusive. Furthermore, previous studies have focused on adults or used a categorical approach to assess depression. The current study looks to identify grey matter volumes (GMV) that predict depressive symptomatology across a clinically concerning sample of adolescents. Methods: Structural MRI data were collected from 338 clinically concerning adolescents (mean age = 15.30 SD=2.07; mean IQ = 101.01 SD=12.43; 132 F). Depression symptoms were indexed via the Mood and Feelings Questionnaire (MFQ). Freesurfer was used to parcellate the brain into 68 cortical regions and 14 subcortical regions. GMV was extracted from all 82 brain areas. Multiple linear regression was used to look at the relationship between MFQ scores and region-specific GMV parameter. Follow up regressions were conducted to look at potential effects of psychiatric diagnoses and medication intake. Results: Our regression analysis produced a significant model (R2 = 0.446, F(86, 251) = 2.348, p \u3c 0.001). Specifically, there was a negative association between GMV of the left parahippocampal (B = -0.203, p = 0.005), right rostral anterior cingulate (B = -0.162, p = 0.049), and right frontal pole (B = -0.147, p = 0.039) and a positive association between GMV of the left bank of the superior temporal sulcus (B = 0.173, p = 0.029). Follow up analyses produced results proximal to the main analysis. Conclusions: Altered regional brain volumes may serve as biomarkers for the development of depressive symptoms during adolescence. These findings suggest a homogeneity of altered cortical structures in adolescents with depressive symptoms

Title: Melatonin, hypnotics and their association with fracture: a matched cohort study

Objectivesalthough melatonin prescribing in England has been increasing in recent years, there have been no large scale studies on the safety of melatonin compared to other medical treatments for insomnia. The primary aim of this study was to examine the association between exposure to melatonin, hypnotic benzodiazepines (temazepam, nitrazepam) or Z-drugs (zolpidem, zopiclone) and fracture risk.Designretrospective cohort study.Setting309 general practices contributing to The Health Improvement Network (THIN) between 2008 and 2013.Participants1,377 patients aged 45 years and older prescribed melatonin; 880 patients prescribed hypnotic benzodiazepines; 1,148 patients prescribed Z-drugs and 2,752 unexposed controls matched by age, gender and practice.Main outcomefracture following prescription of study drugs ascertained from practice records.Resultsthe unadjusted hazard ratios for fracture during the follow-up period were 1.90 (95% CI 1.41–2.57) for melatonin, 1.70 (95% CI 1.18–2.46) for hypnotic benzodiazepines and 2.03 (95% CI 1.45–2.84) for Z-drugs. After adjustment for 26 covariates, the hazard ratios were 1.44 (95% CI 1.01–2.04) for melatonin, 1.26 (95% CI 0.82–1.92) for hypnotic benzodiazepines and 1.52 (95% CI 1.04–2.23) for Z-drugs. Only patients with three or more melatonin prescriptions had elevated risk. The mean time to fracture was 1.04 years and there was no significant difference in mean time to fracture between the cohorts.Conclusionsin this large cohort of patients attending UK primary care, prescriptions for melatonin and Z-drugs were associated with a significantly increased risk of fracture. With the use of melatonin increasing steadily overtime, this study adds to the literature on the safety profile of this drug

Why are eligible patients not prescribed aspirin in primary care? A qualitative study indicating measures for improvement

BACKGROUND: Despite evidence-based guidelines, aspirin prescribing for the secondary prevention of stroke is sub-optimal. Little is known about why general practitioners do not prescribe aspirin to indicated patients. We sought to identify and describe factors that lead general practitioners (GPs) not to prescribe aspirin to eligible stroke patients. This was the first stage of a study exploring the need for and means of improving levels of appropriate aspirin prescribing. METHOD: Qualitative interviews with 15 GPs in the West Midlands. RESULTS: Initially, many GPs did not regard their prescribing as difficult or sub-optimal. However on reflection, they gave several reasons that lead to them not prescribing aspirin for eligible patients or being uncertain. These include: difficulties in applying generic guidelines to individuals presenting in consultations, patient resistance to taking aspirin, the prioritisation of other issues in a time constrained consultation and problems in reviewing the medication of existing stroke patients. CONCLUSION: In order to improve levels of appropriate aspirin prescribing, the nature and presentation risk information available to GPs and patients must be improved. GPs need support in assessing the risks and benefits of prescribing for patients with combinations of complicating risk factors, while means of facilitating improved GP-patient dialogue are required to help address patient uncertainty. A decision analysis based support system is one option. Decision analysis could synthesise current evidence and identify risk data for a range of patient profiles commonly presenting in primary care. These data could then be incorporated into a user-friendly computerised decision support system to help facilitate improved GP-patient communication. Measures of optimum prescribing based upon aggregated prescribing data must be interpreted with caution. It is not possible to assess whether low levels of prescribing reflect appropriate or inappropriate use of aspirin in specific patients where concordance between the GP and the patient is practised

Deep Sequencing of B Cell Receptor Repertoires From COVID-19 Patients Reveals Strong Convergent Immune Signatures.

Deep sequencing of B cell receptor (BCR) heavy chains from a cohort of 31 COVID-19 patients from the UK reveals a stereotypical naive immune response to SARS-CoV-2 which is consistent across patients. Clonal expansion of the B cell population is also observed and may be the result of memory bystander effects. There was a strong convergent sequence signature across patients, and we identified 1,254 clonotypes convergent between at least four of the COVID-19 patients, but not present in healthy controls or individuals following seasonal influenza vaccination. A subset of the convergent clonotypes were homologous to known SARS and SARS-CoV-2 spike protein neutralizing antibodies. Convergence was also demonstrated across wide geographies by comparison of data sets between patients from UK, USA, and China, further validating the disease association and consistency of the stereotypical immune response even at the sequence level. These convergent clonotypes provide a resource to identify potential therapeutic and prophylactic antibodies and demonstrate the potential of BCR profiling as a tool to help understand patient responses

ATP and its N6-substituted analogues: parameterization, molecular dynamics simulation and conformational analysis

In this work we used a combination of classical molecular dynamics and simulated annealing techniques to shed more light on the conformational flexibility of 12 adenosine triphosphate (ATP) analogues in a water environment. We present simulations in AMBER force field for ATP and 12 published analogues [Shah et al. (1997) Proc Natl Acad Sci USA 94: 3565–3570]. The calculations were carried out using the generalized Born (GB) solvation model in the presence of the cation Mg2+. The ion was placed at a close distance (2 Å) from the charged oxygen atoms of the beta and gamma phosphate groups of the −3 negatively charged ATP analogue molecules. Analysis of the results revealed the distribution of inter-proton distances H8–H1′ and H8–H2′ versus the torsion angle ψ (C4–N9-C1′–O4′) for all conformations of ATP analogues. There are two gaps in the distribution of torsion angle ψ values: the first is between −30 and 30 degrees and is described by cis-conformation; and the second is between 90 and 175 degrees, which mostly covers a region of anti conformation. Our results compare favorably with results obtained in experimental assays [Jiang and Mao (2002) Polyhedron 21:435–438]

Individual associations of adolescent alcohol use disorder versus cannabis use disorder symptoms in neural prediction error signaling and the response to novelty

Two of the most commonly used illegal substances by adolescents are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) are associated with poorer decision-making in adolescents. In adolescents, level of AUD symptomatology has been negatively associated with striatal reward responsivity. However, little work has explored the relationship with striatal reward prediction error (RPE) representation and the extent to which any augmentation of RPE by novel stimuli is impacted. One-hundred fifty-one adolescents participated in the Novelty Task while undergoing functional magnetic resonance imaging (fMRI). In this task, participants learn to choose novel or non-novel stimuli to gain monetary reward. Level of AUD symptomatology was negatively associated with both optimal decision-making and BOLD response modulation by RPE within striatum and regions of prefrontal cortex. The neural alterations in RPE representation were particularly pronounced when participants were exploring novel stimuli. Level of CUD symptomatology moderated the relationship between novelty propensity and RPE representation within inferior parietal lobule and dorsomedial prefrontal cortex. These data expand on an emerging literature investigating individual associations of AUD symptomatology levels versus CUD symptomatology levels and RPE representation during reinforcement processing and provide insight on the role of neuro-computational processes underlying reinforcement learning/decision-making in adolescents