Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms : A cohort study in late life

The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36). Image acquisition and image analysis for ABC36 were funded by the Alzheimer’s Research Trust (now Alzheimer’s Research UK). A.D.M., C.J.M., S.S., L.J.W., and R.T.S. have received grants from: Chief Scientist Office, Department of Health, Scottish Government; Biotechnology and Biological Sciences Research Council

Brain hyperintensity location determines outcome in the triad of impaired cognition, physical health and depressive symptoms : A cohort study in late life

The authors would like to thank the participants of the Aberdeen 1936 Birth Cohort (ABC36). Image acquisition and image analysis for ABC36 were funded by the Alzheimer’s Research Trust (now Alzheimer’s Research UK). A.D.M., C.J.M., S.S., L.J.W., and R.T.S. have received grants from: Chief Scientist Office, Department of Health, Scottish Government; Biotechnology and Biological Sciences Research Council

On the mobility, membrane location and functionality of mechanosensitive channels in Escherichia coli

We thank Frans Bianchi and Franz Ho for assistance with molecular cloning, Tim Rasmussen for providing the pTRC-MscK plasmid, Andrew Robinson for providing the pBAD-mEos3.2 plasmid, Matthias Heinemann for assistance with the flow cytometry measurements, Paul Schavemaker for performing Smoldyn simulations and Michiel Punter for programming ImageJ plugins for PALM reconstructions and single-particle tracking. We thank Ian Booth for critical reading of the manuscript, and Christoffer Åberg and Matteo Gabba for valuable discussions. The authors would like to thank David Dryden and Marcel Reuter for performing preliminary experiments from which this work has been built. The work was funded by the EU FP7 ITN-network program NICHE.

Drug prescribing patterns in the General Medical Services Scheme in Ireland and projected costs to 2026

The primary objective is to investigate the main factors contributing to GMS expenditure on pharmaceutical prescribing and projecting this expenditure to 2026. This study is located in the area of pharmacoeconomic cost containment and projections literature. The thesis has five main aims: 1. To determine the main factors contributing to GMS expenditure on pharmaceutical prescribing. 2. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2006 Central Statistics Office (CSO) Census data and 2007 Health Service Executive{Primary Care Reimbursement Service (HSE{PCRS) sample data. 3. To develop a model to project GMS prescribing expenditure in five year intervals to 2026, using 2012 HSE{PCRS population data, incorporating cost containment measures, and 2011 CSO Census data. 4. To investigate the impact of demographic factors and the pharmacology of drugs (Anatomical Therapeutic Chemical (ATC)) on GMS expenditure. 5. To explore the consequences of GMS policy changes on prescribing expenditure and behaviour between 2008 and 2014. The thesis is centered around three published articles and is located between the end of a booming Irish economy in 2007, a recession from 2008{2013, to the beginning of a recovery in 2014. The literature identified a number of factors influencing pharmaceutical expenditure, including population growth, population aging, changes in drug utilisation and drug therapies, age, gender and location. The literature identified the methods previously used in predictive modelling and consequently, the Monte Carlo Simulation (MCS) model was used to simulate projected expenditures to 2026. Also, the literature guided the use of Ordinary Least Squares (OLS) regression in determining demographic and pharmacology factors influencing prescribing expenditure. The study commences against a backdrop of growing GMS prescribing costs, which has risen from e250 million in 1998 to over e1 billion by 2007. Using a sample 2007 HSE{PCRS prescribing data (n=192,000) and CSO population data from 2008, (Conway et al., 2014) estimated GMS prescribing expenditure could rise to e2 billion by2026. The cogency of these findings was impacted by the global economic crisis of 2008, which resulted in a sharp contraction in the Irish economy, mounting fiscal deficits resulting in Ireland's entry to a bailout programme. The sustainability of funding community drug schemes, such as the GMS, came under the spotlight of the EU, IMF, ECB (Trioka), who set stringent targets for reducing drug costs, as conditions of the bailout programme. Cost containment measures included: the introduction of income eligibility limits for GP visit cards and medical cards for those aged 70 and over, introduction of co{payments for prescription items, reductions in wholesale mark{up and pharmacy dispensing fees. Projections for GMS expenditure were reevaluated using 2012 HSE{PCRS prescribing population data and CSO population data based on Census 2011. Taking into account both cost containment measures and revised population predictions, GMS expenditure is estimated to increase by 64%, from e1.1 billion in 2016 to e1.8 billion by 2026, (ConwayLenihan and Woods, 2015). In the final paper, a cross{sectional study was carried out on HSE{PCRS population prescribing database (n=1.63 million claimants) to investigate the impact of demographic factors, and the pharmacology of the drugs, on GMS prescribing expenditure. Those aged over 75 (ẞ = 1:195) and cardiovascular prescribing (ẞ = 1:193) were the greatest contributors to annual GMS prescribing costs. Respiratory drugs (Montelukast) recorded the highest proportion and expenditure for GMS claimants under the age of 15. Drugs prescribed for the nervous system (Escitalopram, Olanzapine and Pregabalin) were highest for those between 16 and 64 years with cardiovascular drugs (Statins) were highest for those aged over 65. Females are more expensive than males and are prescribed more items across the four ATC groups, except among children under 11, (ConwayLenihan et al., 2016). This research indicates that growth in the proportion of the elderly claimants and associated levels of cardiovascular prescribing, particularly for statins, will present difficulties for Ireland in terms of cost containment. Whilst policies aimed at cost containment (co{payment charges, generic substitution, reference pricing, adjustments to GMS eligibility) can be used to curtail expenditure, health promotional programs and educational interventions should be given equal emphasis. Also policies intended to affect physicians prescribing behaviour include guidelines, information (about price and less expensive alternatives) and feedback, and the use of budgetary restrictions could yield savings.

“Medical bag for General Practice” Just in Case: redesigning the doctor’s bag (2012)

This research addressed practice related problems from a medico-legal perspective and aims to provide a working tool that aids GPs to comply with best practice protocols. The resulting bag was developed in collaboration with General Practitioners, clinicians and members of the Medical Defense Union. Using proven methods developed within the Healthcare & Patient Safety Lab (e.g. DOME, Ambulance) to establish an evidence-based brief, this research used task, equipment and consumables analysis to determine minimum requirements and preferred layouts for task optimisation. The research established that clinicians require three distinct functions in their workspace: laying out, organisation and information retrieval. Feedback from clinicians indicates that this working tool allows them to access information and equipment wherever they may be and suggests an improvement from current practice. The research is now into a second year where the design of the bag will be refined and tested. Lifestyle and demographic changes such as the ageing population and increased prevalence of chronic diseases require more consistent standards of primary care, and care that is well coordinated and integrated (Imison, et al., 2011). Many guidelines exist relating to general practice and the doctor’s bag (NSLMC, 2008, RACGP, 2010, RCGP, 2008 and Hiramanek, 2004), however there is no standard in the UK that regulates the shape and materials of the bag or its contents. Doctors may use any sort of vessel to transport their equipment and consumables to a patient’s location. Furthermore, treating a patient in their own home, outside an ideal clinical environment, presents its own complications. A looks-like, works-like bag prototype and information system that will be used in clinical trials, the results of which will determine the manufacturing of a new, standardised bag for clinical treatment used by members of the Medical Defence Union.

Evaluation Of The Location Of Capsules Swallowed With Food During The Pharyngeal Phase Triggering In Asymptomatic Adults.

To assess the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. The location of the bolus during the pharyngeal phase triggering provides information about the sensorimotor model of the beginning of deglutition onset. To evaluate the location of hard gelatin capsules in the pharyngeal phase triggering among asymptomatic adults. A videofluoroscopy swallowing study was carried out in 60 subjects (14 male and 46 female participants) aged between 27 and 55 years, who were evaluated with hard gelatin capsules #00 and #3 containing barium sulfate, swallowed with liquid food and pudding, in free volume. The first laryngeal elevation movement was the criterion to locate the pharyngeal phase triggering. Statistical analysis was based on the McNemar test. Capsule #3 presented higher percentage of location in the tongue dorsum compared to capsule #00, and capsule #00 presented higher percentage of location in the tongue base and vallecula compared to capsule #3. There was a difference between different capsules swallowed with liquid (p=0.016) and pudding (p=0.037). The capsule size influenced the location of the pharyngeal phase triggering. Smaller capsules started pharyngeal phase in the most anterior region (tongue dorsum) compared to larger capsules.

Motivating Medical Students To Learn Basic Science Concepts Using Chronic Myeloid Leukemia As An Integration Theme.

To report on the use of chronic myeloid leukemia as a theme of basic clinical integration for first year medical students to motivate and enable in-depth understanding of the basic sciences of the future physician. During the past thirteen years we have reviewed and updated the curriculum of the medical school of the Universidade Estadual de Campinas. The main objective of the new curriculum is to teach the students how to learn to learn. Since then, a case of chronic myeloid leukemia has been introduced to first year medical students and discussed in horizontal integration with all themes taught during a molecular and cell biology course. Cell structure and components, protein, chromosomes, gene organization, proliferation, cell cycle, apoptosis, signaling and so on are all themes approached during this course. At the end of every topic approached, the students prepare in advance the corresponding topic of clinical cases chosen randomly during the class, which are then presented by them. During the final class, a paper regarding mutations in the abl gene that cause resistance to tyrosine kinase inhibitors is discussed. After each class, three tests are solved in an interactive evaluation. The course has been successful since its beginning, 13 years ago. Great motivation of those who participated in the course was observed. There were less than 20% absences in the classes. At least three (and as many as nine) students every year were interested in starting research training in the field of hematology. At the end of each class, an interactive evaluation was performed and more than 70% of the answers were correct in each evaluation. Moreover, for the final evaluation, the students summarized, in a written report, the molecular and therapeutic basis of chronic myeloid leukemia, with scores ranging from 0 to 10. Considering all 13 years, a median of 78% of the class scored above 5 (min 74%-max 85%), and a median of 67% scored above 7. Chronic myeloid leukemia is an excellent example of a disease that can be used for clinical basic integration as this disorder involves well known protein, cytogenetic and cell function abnormalities, has well-defined diagnostic strategies and a target oriented therapy.

Mentors, students, and the undergraduate medical course: a virtuous circle

BACKGROUND: Mentoring Programs have been developed in several medical schools, but few studies have investigated the mentors'perspective. PURPOSES: To explore mentors'perceptions regarding their experience. METHODS: Mentors at a medical school were invited to participate in an in-depth interview including questions on satisfaction, difficulties, and perception of changes resulting from the program. RESULTS: Mentors' satisfaction and difficulties are strongly associated with students'involvement in the activity. Mentors believe changes observed in students were more related to life issues; for some mentors, there is no recognition or awareness of the program. However, most of the mentors acknowledged important changes in relation to themselves: as teachers, faculty members, and individuals. CONCLUSION: Attendance is crucial for both the mentoring relationship and strengthening of the program. Students involved in the activity motivate mentors in teaching and curriculum development, thereby creating a virtuous circle and benefiting undergraduate medical education as a whole.

Evidence for divided automatic attention

A long-standing debate in the literature is whether attention can form two or more independent spatial foci in addition to the well-known unique spatial focus. There is evidence that voluntary visual attention divides in space. The possibility that this also occurs for automatic visual attention was investigated here. Thirty-six female volunteers were tested. In each trial, a prime stimulus was presented in the left or right visual hemifield. This stimulus was characterized by the blinking of a superior, middle or inferior ring, the blinking of all these rings, or the blinking of the superior and inferior rings. A target stimulus to which the volunteer should respond with the same side hand or a target stimulus to which she should not respond was presented 100 ms later in a primed location, a location between two primed locations or a location in the contralateral hemifield. Reaction time to the positive target stimulus in a primed location was consistently shorter than reaction time in the horizontally corresponding contralateral location. This attentional effect was significantly smaller or absent when the positive target stimulus appeared in the middle location after the double prime stimulus. These results suggest that automatic visual attention can focus on two separate locations simultaneously, to some extent sparing the region in between.

Drug consumption among medical students in São Paulo, Brazil: influences of gender and academic year

OBJECTIVE: To analyze alcohol, tobacco and other drug use among medical students. METHOD: Over a five-year period (1996-2001), we evaluated 457 students at the Universidade de São Paulo School of Medicine, located in São Paulo, Brazil. The students participated by filling out an anonymous questionnaire on drug use (lifetime, previous 12 months and previous 30 days). The influence that gender and academic year have on drug use was also analyzed. RESULTS: During the study period, there was an increase in the use of illicit drugs, especially inhalants and amphetamines, among the medical students evaluated. Drug use (except that of marijuana and inhalants) was comparable between the genders, and academic year was an important influencing factor. DISCUSSION: Increased inhalant use was observed among the medical students, especially among males and students in the early undergraduate years. This is suggestive of a specific behavioral pattern among medical students. Our findings corroborate those of previous studies. CONCLUSION: Inhalant use is on the rise among medical students at the Universidade de São Paulo School of Medicine. Because of the negative health effects of illicit drug use, further studies are needed in order to deepen the understanding of this phenomenon and to facilitate the development of preventive measures.

Cytogenetic analysis of Astylus antis (Perty, 1830) (Coleoptera, Melyridae): Karyotype, heterochromatin and location of ribosomal genes

Cytogenetic analysis of Astylus antis using mitotic and meiotic cells was performed to characterize the haploid and diploid numbers, sex determination system, chromosome morphology, constitutive heterochromatin distribution pattern and chromosomes carrying nucleolus organizer regions (NORs). Analysis of spermatogonial metaphase cells revealed the diploid number 2n = 18, with mostly metacentric chromosomes. Metaphase I cells exhibited 2n = 8II+Xyp and a parachute configuration of the sex chromosomes. Spermatogonial metaphase cells submitted to C-banding showed the presence of small dots of constitutive heterochromatin in the centromeric regions of nearly all the autosomes and on the short arm of the X chromosome (Xp), as well as an additional band on one of the arms of pair 1. Mitotic cells submitted to double staining with base-specific fluorochromes (DAPI-CMA3) revealed no regions rich in A+T or G+C sequences. Analysis of spermatogonial mitotic cells after sequential Giemsa/AgNO3 staining did not reveal any specific mark on the chromosomes. Meiotic metaphase I cells stained with silver nitrate revealed a strong impregnation associated to the sex chromosomes, and in situ hybridization with an 18S rDNA probe showed ribosomal cistrons in an autosomal bivalent.

A scientific note: Foragers deposit attractive scent marks in a stingless bee that does not communicate food location

National Science Foundation NSF IBN[0316697]

Oral Health Promotion Through an Online Training Program for Medical Students

The objective of this study was to compare the impact on knowledge and counseling skills of face-to-face and Internet-based oral health training programs on medical students. Participants consisted of 148 (82 percent) of the 180 invited students attending their fifth academic year at the Faculty of Medicine, University of Sao Paulo, Brasil, in 2007. The interventions took place during a three-month training period in the clinical Center for Health Promotion, which comprised part of a clerkship in Internal Medicine. The students were divided into four groups: 1) Control Group (Control), with basic intervention; 2) Brochure Group (Br), with basic intervention plus complete brochure with oral health themes; 3) Cybertutor Group (Cy), with basic intervention plus access to an Internet-based training program about oral health themes; and 4) Cybertutor + Contact Group (Cy+C), the same as Cy plus brief proactive contact with a tutor. The impact of these interventions on student knowledge was measured with pre- and post assessments, and student skills in asking and counseling about oral health were assessed with an objective structured clinical examination (OSCE). Multivariate logistic regression models were applied to identify the odds ratios of scoring above Control's medians on the final assessment and the OSCE. In the results, Cy+C performed significantly better than Control on both the final assessment (OR 9.4; 95% CI 2.7-32.8) and the OSCE (OR 5.6; 95% CI 1.9-16.3) and outperformed all the other groups. The Cy+C group showed the most significant increase in knowledge and the best skills in asking and counseling about oral health.

The characteristics of depressive symptoms in medical students during medical education and training: a cross-sectional study

Background: Medical education and training can contribute to the development of depressive symptoms that might lead to possible academic and professional consequences. We aimed to investigate the characteristics of depressive symptoms among 481 medical students (79.8% of the total who matriculated). Methods: The Beck Depression Inventory (BDI) and cluster analyses were used in order to better describe the characteristics of depressive symptoms. Medical education and training in Brazil is divided into basic (1(st) and 2(nd) years), intermediate (3(rd) and 4(th) years), and internship (5(th) and 6(th) years) periods. The study organized each item from the BDI into the following three clusters: affective, cognitive, and somatic. Statistical analyses were performed using analysis of variance (ANOVA) with post-hoc Tukey corrected for multiple comparisons. Results: There were 184 (38.2%) students with depressive symptoms (BDI > 9). The internship period resulted in the highest BDI scores in comparison to both the basic (p < .001) and intermediate (p < .001) periods. Affective, cognitive, and somatic clusters were significantly higher in the internship period. An exploratory analysis of possible risk factors showed that females (p = .020) not having a parent who practiced medicine (p = .016), and the internship period (p = .001) were factors for the development of depressive symptoms. Conclusion: There is a high prevalence towards depressive symptoms among medical students, particularly females, in the internship level, mainly involving the somatic and affective clusters, and not having a parent who practiced medicine. The active assessment of these students in evaluating their depressive symptoms is important in order to prevent the development of co-morbidities and suicide risk.

Genetic Background of Patients from a University Medical Center in Manhattan: Implications for Personalized Medicine

Background: The rapid progress currently being made in genomic science has created interest in potential clinical applications; however, formal translational research has been limited thus far. Studies of population genetics have demonstrated substantial variation in allele frequencies and haplotype structure at loci of medical relevance and the genetic background of patient cohorts may often be complex. Methods and Findings: To describe the heterogeneity in an unselected clinical sample we used the Affymetrix 6.0 gene array chip to genotype self-identified European Americans (N = 326), African Americans (N = 324) and Hispanics (N = 327) from the medical practice of Mount Sinai Medical Center in Manhattan, NY. Additional data from US minority groups and Brazil were used for external comparison. Substantial variation in ancestral origin was observed for both African Americans and Hispanics; data from the latter group overlapped with both Mexican Americans and Brazilians in the external data sets. A pooled analysis of the African Americans and Hispanics from NY demonstrated a broad continuum of ancestral origin making classification by race/ethnicity uninformative. Selected loci harboring variants associated with medical traits and drug response confirmed substantial within-and between-group heterogeneity. Conclusion: As a consequence of these complementary levels of heterogeneity group labels offered no guidance at the individual level. These findings demonstrate the complexity involved in clinical translation of the results from genome-wide association studies and suggest that in the genomic era conventional racial/ethnic labels are of little value.