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1.  Professionals: Their Problems, Their Fears, and Their Social Responsibilities * 
Professional societies have been reluctant to enter actively into the public processes by which decisions are made on economic, social, and political issues. This reluctance comes from (1) fears about the status of the profession and the professional society, (2) fears about economic reprisal, (3) potential conflicts between the goals of a philosophy of trade unionism and the goals of a philosophy of professional social responsibility, and (4) domination of some professional societies by nonprofessional business, industrial, or administrative groups. This reluctance has been justified by the development of a myth that the professional can exercise individual social responsibility while maintaining the neutrality of his institutions and societies. This myth must be ignored because our public decision-making processes can only function properly if groups, such as professional societies, actively enter that decision-making process.
PMCID: PMC198602  PMID: 4691329
2.  Violence in Jamaica: an analysis of homicides 1998–2002 
Injury Prevention  2006;12(1):15-18.
The aim of the study was to create a profile of Jamaican homicide victims and to describe the circumstances, motives, and the weapons used in homicide incidents. The authors read the police narratives for all Jamaican homicides 1998–2002 and coded them using a predetermined set of variables. Analyses were conducted to describe victim characteristics, motive, and weapon use. The majority of homicide victims were male (over 89%), and 15–44 years old (80%). The rate of homicide for males age 15–44 years was 121 per 100 000 compared with a rate of 12 per 100 000 for females in the same age group. The main motives for homicide were disputes (29%) and reprisals (30%). Gunshot wounds were the cause of death in 66% of all homicides. Guns were used primarily in reprisals, robbery, and drug/gang related homicides; in half of all dispute related homicides the perpetrator used a knife. Homicides in Jamaica are not primarily gang or robbery related. Rather, they are mainly caused by arguments or reprisals. Homicide has become a common feature of dispute resolution in Jamaica.
doi:10.1136/ip.2005.010488
PMCID: PMC2563489  PMID: 16461414
violence; homicide; guns; Jamaica
3.  Retrovirology: 3 at age 2 
Retrovirology  2006;3:30.
Retrovirology announces new editorial board members and reprises progress over the first two years of publishing.
doi:10.1186/1742-4690-3-30
PMCID: PMC1483831
4.  Duplex strand joining reactions catalyzed by vaccinia virus DNA polymerase 
Nucleic Acids Research  2006;35(1):143-151.
Vaccinia virus DNA polymerase catalyzes duplex-by-duplex DNA joining reactions in vitro and many features of these recombination reactions are reprised in vivo. This can explain the intimate linkage between virus replication and genetic recombination. However, it is unclear why these apparently ordinary polymerases exhibit this unusual catalytic capacity. In this study, we have used different substrates to perform a detailed investigation of the mechanism of duplex-by-duplex recombination catalyzed by vaccinia DNA polymerase. When homologous, blunt-ended linear duplex substrates are incubated with vaccinia polymerase, in the presence of Mg2+ and dNTPs, the appearance of joint molecules is preceded by the exposure of complementary single-stranded sequences by the proofreading exonuclease. These intermediates anneal to form a population of joint molecules containing hybrid regions flanked by nicks, 1–5 nt gaps, and/or short overhangs. The products are relatively resistant to exonuclease (and polymerase) activity and thus accumulate in joining reactions. Surface plasmon resonance (SPR) measurements showed the enzyme has a relative binding affinity favoring blunt-ended duplexes over molecules bearing 3′-recessed gaps. Recombinant duplexes are the least favored ligands. These data suggest that a particular combination of otherwise ordinary enzymatic and DNA-binding properties, enable poxvirus DNA polymerases to promote duplex joining reactions.
doi:10.1093/nar/gkl1015
PMCID: PMC1802553  PMID: 17158165
5.  Some current factors influencing the prescribing and use of psychiatric drugs. 
Public Health Reports  1992;107(1):47-53.
A reprise of selected known factors about the influences affecting the prescribing and use of drugs, and some new developments in the drug marketplace, are the basis for this summary and observations about future expectations regarding psychotherapeutic agents. This information can be used to assist in formulating or updating, or both, conceptualizations and hypotheses for future policy and research planning in this area.
PMCID: PMC1403600  PMID: 1738808
6.  The use of alternative medicines by somatoform disorder patients in Spain. 
Somatisation disorder patients show a high rate of alternative medicine consultations but most of them do not disclose this fact to the doctor owing to fear of reprisals. The reasons given for using these medicines do not equate to sociodemographic characteristics, psychiatric diagnosis or personality traits but instead to dissatisfaction with medical care and with diagnosis. These patients appreciate the longer and more frequent consultations as well as the better doctor-patient relationship of alternative medicines.
PMCID: PMC1313731  PMID: 10962791
7.  Doctor–patient sexual relationships in medical oaths 
Journal of Medical Ethics  2006;32(12):702-705.
Background
Doctor–patient sexual relationship is considered to be unfair because the first party would be abusing the second party's vulnerability. The prohibition of this relationship is noted in the Hippocratic oath. Currently, a reprise of the use of oaths in medical schools can be observed.
Aim
To determine whether the prohibition has been maintained and how its expression has varied in the oaths during different periods.
Methods
50 oaths were studied: 13 ancient–medieval and 37 modern–contemporary. Of the 50 texts, 19 were versions of the original oaths. The oaths that pointed out the prohibited doctor–patient relationship referred to any sexual aspect or included paragraphs that began as the Hippocratic oath does were noted.
Results
Of the 24 (48%) texts that expressed the prohibition, 8 (62%) were ancient–medieval and 16 (43%) were modern–contemporary. Some expressly call it Hippocratic oath, many use general terminology (corruption or vice) and others describe it in association with other commitments (abortion and euthanasia).
Conclusions
The clause on the prohibition of the doctor–patient sexual relationship in Hippocratic oath was included to be for legal, economic and social reasons at the time. That the clause is found mostly in the ancient–medieval oaths can be attributed to the influence of the original. This commitment is generalised and associated with others by contemporary formulas. Currently, sexual relationships are the subject of legal and ethical analysis and their inclusion in the oaths is being debated.
doi:10.1136/jme.2005.014910
PMCID: PMC2563341  PMID: 17145909
8.  Archaeosortases and Exosortases Are Widely Distributed Systems Linking Membrane Transit with Posttranslational Modification 
Journal of Bacteriology  2012;194(1):36-48.
Multiple new prokaryotic C-terminal protein-sorting signals were found that reprise the tripartite architecture shared by LPXTG and PEP-CTERM: motif, TM helix, basic cluster. Defining hidden Markov models were constructed for all. PGF-CTERM occurs in 29 archaeal species, some of which have more than 50 proteins that share the domain. PGF-CTERM proteins include the major cell surface protein in Halobacterium, a glycoprotein with a partially characterized diphytanylglyceryl phosphate linkage near its C terminus. Comparative genomics identifies a distant exosortase homolog, designated archaeosortase A (ArtA), as the likely protein-processing enzyme for PGF-CTERM. Proteomics suggests that the PGF-CTERM region is removed. Additional systems include VPXXXP-CTERM/archeaosortase B in two of the same archaea and PEF-CTERM/archaeosortase C in four others. Bacterial exosortases often fall into subfamilies that partner with very different cohorts of extracellular polymeric substance biosynthesis proteins; several species have multiple systems. Variant systems include the VPDSG-CTERM/exosortase C system unique to certain members of the phylum Verrucomicrobia, VPLPA-CTERM/exosortase D in several alpha- and deltaproteobacterial species, and a dedicated (single-target) VPEID-CTERM/exosortase E system in alphaproteobacteria. Exosortase-related families XrtF in the class Flavobacteria and XrtG in Gram-positive bacteria mark distinctive conserved gene neighborhoods. A picture emerges of an ancient and now well-differentiated superfamily of deeply membrane-embedded protein-processing enzymes. Their target proteins are destined to transit cellular membranes during their biosynthesis, during which most undergo additional posttranslational modifications such as glycosylation.
doi:10.1128/JB.06026-11
PMCID: PMC3256604  PMID: 22037399
9.  Harvey, by Hercules! The Hero of the Blood’s Circulation 
Medical History  2013;57(1):6-27.
This article continues the analyses in Medical History 52 (2008), 73–90, 365–86 of William Harvey’s self-understanding as the philosopher and discoverer of the blood’s circulation. Harvey brilliantly and subversively assumed the persona of the mythological Hercules to embody his own anatomical labour in De motu cordis et sanguinis (1628). He reprised the role in self-defence against accusations in the College of Physicians, London, of his breach of faith with medical tradition. Harvey sought to usurp the medical epithet ‘a second Hercules’ by reforming humanist dependence on ancient texts as authoritative medicine. A knowledge of the theory and practice of Renaissance humanism discloses his identification with the Herculean labour of cleansing the Augean stable. He employed anatomical demonstration against Galen’s porous cardiac septum, which admitted blood across the ventricles. Harvey’s oath mehercule swore against Galen’s Dia to assert the necessity of opening an alternate route for the blood flow. His Herculean labour was to dam the cardiac septum and divert the blood flow into a continuous channel through the arteries and veins. His circulation of the blood also imitated Hercules’ successful dependence on the force of the water flow to flush the Augean stable. Harvey’s copia did not denote a quantitative amount but a powerful supply. Harvey aspired to be, like Hercules, immortal, a term which the College belatedly acknowledged. This cultural analysis exposes Harvey’s professional issues and personal ambitions, so to promote a fuller understanding of his historic role in medical discovery.
doi:10.1017/mdh.2012.78
PMCID: PMC3566748  PMID: 23393400
William Harvey; Blood; Circulation of; Septum; Hercules; Augean Stables; Swearing
10.  The Importance of International Medical Rotations in Selection of an Otolaryngology Residency 
Background
The objective of this study was to determine the extent of interest in international electives among prospective otolaryngology residents and to determine whether the availability of international electives affected students' interest in ranking a particular residency program.
Methods
A 3-part survey was given to all medical students enrolled in the 2008 otolaryngology match via the Electronic Residency Application Service. Part 1 elicited demographic information. Part 2 explored general interest in international rotations. Part 3 involved ranking several factors affecting students' choice of residency programs. This survey was developed at our institution, with no formal validation. Participation was anonymous and voluntary.
Results
A total of 307 students entered the otolaryngology match, and 55 surveys (18%) were completed. Twenty-five of 55 students (55%) had completed an international elective during or prior to medical school, and 51 of 55 respondents (93%) had a “strong” or “very strong” desire to participate in an international elective during residency; 48 of 55 students (87%) had a “strong” or “very strong” desire to participate in international surgical missions after residency. Future practice goals had no correlation with interest in international rotations, either during or after residency training. Respondents ranked 8 factors that had an impact on residency program selection in the following order of importance: operative experience, location, lifestyle, research opportunities, didactics, international electives, prestige of program, and salary.
Conclusion
Interest in international medicine among prospective otolaryngologists was high in this subset of respondents but did not appear to affect residency program selection.
doi:10.4300/JGME-D-10-00185.1
PMCID: PMC3179233  PMID: 22942976
11.  Clinical research and global health: Mentoring the next generation of health care students 
Global public health  2011;6(3):234-246.
Interest in global health and opportunities to conduct clinical research at international sites have increased markedly for health profession trainees. With this increase in demand comes an increase in the need for mentors at international and home institutions to provide guidance with designing, implementing, and analysing clinical research projects that benefit both the trainees and the research site. In this article, we provide an overview of our insights gained through mentoring in the international setting and suggest a series of key points to help ensure an enjoyable and productive international clinical research experience for both trainees and mentors.
doi:10.1080/17441692.2010.494248
PMCID: PMC2958226  PMID: 20635270
clinical research; mentoring; global health
12.  A Method to Determine the Ionization Efficiency Change of Peptides Caused by Phosphorylation 
Quantitative assessment of post-translational modifications in proteins by mass spectrometry often requires the consideration of the alteration in ionization efficiency of peptides induced by the modification. Herein, we introduced a method to measure the relative ionization efficiencies of peptides using specifically designed unlabeled peptides. In our design, the peptide under study, in either the unmodified or modified form, is linked with an internal standard peptide via an enzyme cleavage site; thus, after enzymatic digestion, we could obtain readily a 1:1 ratio between the peptide under investigation and the internal standard peptide. The relative ionization efficiencies of the modified and unmodified peptides can then be calculated from the modification-induced change in the ratio of relative abundances of the ion of the peptide of interest over that of the internal standard peptide. We demonstrated the usefulness of the method by assessing the change in ionization efficiencies of four peptides introduced by phosphorylation.
doi:10.1016/j.jasms.2007.08.010
PMCID: PMC2093959  PMID: 17870613
13.  “Working the System”—British American Tobacco's Influence on the European Union Treaty and Its Implications for Policy: An Analysis of Internal Tobacco Industry Documents 
PLoS Medicine  2010;7(1):e1000202.
Katherine Smith and colleagues investigate the ways in which British American Tobacco influenced the European Union Treaty so that new EU policies advance the interests of major corporations, including those that produce products damaging to health.
Background
Impact assessment (IA) of all major European Union (EU) policies is now mandatory. The form of IA used has been criticised for favouring corporate interests by overemphasising economic impacts and failing to adequately assess health impacts. Our study sought to assess how, why, and in what ways corporations, and particularly the tobacco industry, influenced the EU's approach to IA.
Methods and Findings
In order to identify whether industry played a role in promoting this system of IA within the EU, we analysed internal documents from British American Tobacco (BAT) that were disclosed following a series of litigation cases in the United States. We combined this analysis with one of related literature and interviews with key informants. Our analysis demonstrates that from 1995 onwards BAT actively worked with other corporate actors to successfully promote a business-oriented form of IA that favoured large corporations. It appears that BAT favoured this form of IA because it could advance the company's European interests by establishing ground rules for policymaking that would: (i) provide an economic framework for evaluating all policy decisions, implicitly prioritising costs to businesses; (ii) secure early corporate involvement in policy discussions; (iii) bestow the corporate sector with a long-term advantage over other actors by increasing policymakers' dependence on information they supplied; and (iv) provide businesses with a persuasive means of challenging potential and existing legislation. The data reveal that an ensuing lobbying campaign, largely driven by BAT, helped secure binding changes to the EU Treaty via the Treaty of Amsterdam that required EU policymakers to minimise legislative burdens on businesses. Efforts subsequently focused on ensuring that these Treaty changes were translated into the application of a business orientated form of IA (cost–benefit analysis [CBA]) within EU policymaking procedures. Both the tobacco and chemical industries have since employed IA in apparent attempts to undermine key aspects of European policies designed to protect public health.
Conclusions
Our findings suggest that BAT and its corporate allies have fundamentally altered the way in which all EU policy is made by making a business-oriented form of IA mandatory. This increases the likelihood that the EU will produce policies that advance the interests of major corporations, including those that produce products damaging to health, rather than in the interests of its citizens. Given that the public health community, focusing on health IA, has largely welcomed the increasing policy interest in IA, this suggests that urgent consideration is required of the ways in which IA can be employed to undermine, as well as support, effective public health policies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The primary goal of public health, the branch of medicine concerned with the health of communities, is to improve lives by preventing disease. Public-health groups do this by assessing and monitoring the health of communities, by ensuring that populations have access to appropriate and cost-effective health care, and by helping to formulate public policies that safeguard human health. Until recently, most of the world's major public-health concerns related to infectious diseases. Nowadays, however, many major public-health concerns are linked to the goods made and marketed by large corporations such as fast food, alcohol, tobacco, and chemicals. In Europe, these corporations are regulated by policies drawn up both by member states and by the European Commission, the executive organ of the European Union (EU; an economic and political partnership among 27 democratic European countries). Thus, for example, the tobacco industry, which is widely recognized as a driver of the smoking epidemic, is regulated by Europe-wide tobacco control policies and member state level policies.
Why Was This Study Done?
Since 1997, the European Commission has been required by law to assess the economic, social (including health), and environmental consequences of new policy initiatives using a process called an “impact assessment” (IA). Because different types of IA examine the likely effects of policies on different aspects of daily life—a health impact assessment, for example, focuses on a policy's effect on health—the choice of IA can lead to different decisions being taken about new policies. Although the IA tool adopted by the European Commission aims to assess economic, environmental and social impacts, independent experts suggest this tool does not adequately assess health impacts. Instead, economic impacts receive the most attention, a situation that may favour the interests of large businesses. In this study, the researchers seek to identify how and why the EU's approach to IA developed. More specifically, the researchers analyze internal documents from British American Tobacco (BAT), which have been disclosed because of US litigation cases, to find out whether industry has played a role in promoting the EU's system of IA.
What Did the Researchers Do and Find?
The researchers analyzed 714 BAT internal documents (identified by searching the Legacy Tobacco Documents Library, which contains more than 10 million internal tobacco company documents) that concerned attempts made by BAT to influence regulatory reforms in Europe. They also analyzed related literature from other sources (for example, academic publications) and interviewed 16 relevant people (including people who had worked at the European Commission). This analysis shows that from 1995, BAT worked with other businesses to promote European regulatory reforms (in particular, the establishment of a business-orientated form of IA) that favor large corporations. A lobbying campaign, initiated by BAT but involving a “policy network” of other companies, first helped to secure binding changes to the EU Treaty that require policymakers to minimize legislative burdens on businesses. The analysis shows that after achieving this goal, which BAT described as an “important victory,” further lobbying ensured that these treaty changes were translated into the implementation of a business-orientated form of IA within the EU. Both the tobacco industry and the chemical industry, the researchers argue, have since used the IA to delay and/or weaken EU legislation intended to protect public health.
What Do These Findings Mean?
These findings suggest that BAT and its corporate allies have fundamentally altered the way in which EU policy is made by ensuring that all significant EU policy decisions have to be assessed using a business-orientated IA. As the authors note, this situation increases the likelihood that the EU will produce policies that favor big business rather than the health of its citizens. Furthermore, these findings suggest that by establishing a network of other industries to help in lobbying for EU Treaty changes, BAT was able to distance itself from the push to establish a business-orientated IA to the extent that Commission officials were unaware of the involvement of the tobacco industry in campaigns for IA. Thus, in future, to safeguard public health, policymakers and public-health groups must pay more attention to corporate efforts to shape decision-making processes. In addition, public-health groups must take account of the ways in which IA can be used to undermine as well as support effective public-health policies and they must collaborate more closely in their efforts to ensure effective national and international policy.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/0.1371/journal.pmed.1000202.
Wikipedia has a page on public health (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
More information on the European Union (in several languages), on public health in the European Union, and on impact assessment by the European Commission is available
The Legacy Tobacco Documents Library is a public, searchable database of tobacco company internal documents detailing their advertising, manufacturing, marketing, sales, and scientific activities
The World Health Organization provides information about the dangers of tobacco (in several languages)
The Smoke Free Partnership contains more information about smoking prevalence in Europe and about European policies to tackle the public health issues associated with tobacco use
For more information about tobacco industry influence on policy see the 2009 World Health Organization report on tobacco industry interference with tobacco control
doi:10.1371/journal.pmed.1000202
PMCID: PMC2797088  PMID: 20084098
14.  Parasitic Infections: A Role for C-Type Lectins Receptors 
BioMed Research International  2013;2013:456352.
Antigen-presenting cells (APCs) sense the microenvironment through several types of receptors that recognize pathogen-associated molecular patterns. In particular, C-type lectins receptors (CLRs), which are expressed by distinct subsets of dendritic cells (DCs) and macrophages (MØs), recognize and internalize specific carbohydrate antigens in a Ca2+-dependent manner. The targeting of these receptors is becoming an efficient strategy for parasite recognition. However, relatively little is known about how CLRs are involved in both pathogen recognition and the internalization of parasites. The role of CLRs in parasite infections is an area of considerable interest because this research will impact our understanding of the initiation of innate immune responses, which influences the outcome of specific immune responses. This paper attempts to summarize our understanding of the effects of parasites' interactions with CLRs.
doi:10.1155/2013/456352
PMCID: PMC3581113
15.  Inferring evolution of gene duplicates using probabilistic models and nonparametric belief propagation 
BMC Genomics  2013;14(Suppl 1):S15.
Background
Gene duplication, followed by functional evolution of duplicate genes, is a primary engine of evolutionary innovation. In turn, gene expression evolution is a critical component of overall functional evolution of paralogs. Inferring evolutionary history of gene expression among paralogs is therefore a problem of considerable interest. It also represents significant challenges. The standard approaches of evolutionary reconstruction assume that at an internal node of the duplication tree, the two duplicates evolve independently. However, because of various selection pressures functional evolution of the two paralogs may be coupled. The coupling of paralog evolution corresponds to three major fates of gene duplicates: subfunctionalization (SF), conserved function (CF) or neofunctionalization (NF). Quantitative analysis of these fates is of great interest and clearly influences evolutionary inference of expression. These two interrelated problems of inferring gene expression and evolutionary fates of gene duplicates have not been studied together previously and motivate the present study.
Results
Here we propose a novel probabilistic framework and algorithm to simultaneously infer (i) ancestral gene expression and (ii) the likely fate (SF, NF, CF) at each duplication event during the evolution of gene family. Using tissue-specific gene expression data, we develop a nonparametric belief propagation (NBP) algorithm to predict the ancestral expression level as a proxy for function, and describe a novel probabilistic model that relates the predicted and known expression levels to the possible evolutionary fates. We validate our model using simulation and then apply it to a genome-wide set of gene duplicates in human.
Conclusions
Our results suggest that SF tends to be more frequent at the earlier stage of gene family expansion, while NF occurs more frequently later on.
doi:10.1186/1471-2164-14-S1-S15
PMCID: PMC3549814  PMID: 23368094
16.  Beyond the Genome 2000: The 18th International Congress of Biochemistry and Molecular Biology 
Yeast (Chichester, England)  2000;17(4):314-321.
The meeting was held on 16–20 July 2000 at the International Convention Centre in Birmingham, UK, and was co-organized by the International Union of Biochemistry and Molecular Biology (IUBMB) and the Federation of European Biochemical Societies (FEBS). Although the meeting had a broad subject area, the emphasis was firmly placed on post-genomic studies, and hence several sessions should be of interest to our readers. We provide highlights of these sessions, bringing you a report on the most exciting and informative presentations.
doi:10.1002/1097-0061(200012)17:4<314::AID-YEA47>3.0.CO;2-K
PMCID: PMC2448388  PMID: 11119309
17.  A pharmacogene database enhanced by the 1000 Genomes Project 
Pharmacogenetics and genomics  2009;19(10):829-832.
Human genetic variation is likely to be responsible for a substantial fraction of the variability in complex traits including drug response. Single nucleotide polymorphisms (SNPs) have been implicated in drug response using genome-wide association studies as well as candidate-gene approaches. A more comprehensive catalogue of human genetic variation should complement the current large-scale genotypic dataset from the International HapMap Project, which focuses on common genetic variants. The 1000 Genomes Project (KGP) is an international research effort that aims to provide the most comprehensive map of human genetic variation using next-generation sequencing platforms. Due to the lack of convenient tools, however, it is a challenge for the pharmacogenetic research community to take advantage of these data. We present here a new database of some pharmacogenes of particular interest to pharmacogenetic researchers. Our database provides a convenient portal for immediate utilization of the newly released KGP data in pharmacogenetic studies.
doi:10.1097/FPC.0b013e3283317bac
PMCID: PMC2935084  PMID: 19745786
pharmacogenetics; pharmacogene; single nucleotide polymorphism; next generation sequencing; database
18.  Surgery and Global Public Health: The UNC-Malawi Surgical Initiative as a Model for Sustainable Collaboration 
World Journal of Surgery  2011;35(1):17-21.
Addressing global health disparities in the developing world gained prominence during the first decade of the twenty-first century. The HIV/AIDS epidemic triggered much interest in and funding for health improvement and mortality reduction in low- and middle-income nations, particularly in sub-Saharan Africa. Alliances between U.S. academic medical centers and African nations were created through the departments of internal medicine and infectious disease. However, the importance of addressing surgical disease as part of global public health is becoming recognized as part of international health development efforts. We propose a novel model to reduce the global burden of surgical diseases in resource poor settings by incorporating a sustained institutional surgical presence with our residency training experience by placing a senior surgical resident to provide continuity of care and facilitate training of local personnel. We present the experiences of the University of North Carolina (UNC) Department of Surgery as part of the UNC Project in Malawi as an example of this innovative approach.
doi:10.1007/s00268-010-0836-2
PMCID: PMC3290403  PMID: 21052998
19.  Rescue of internalization-defective platelet-activating factor receptor function by EBP50/NHERF1 
Platelet-activating factor (PAF) is a potent phospholipid mediator involved in specific disease states such as allergic asthma, atherosclerosis and psoriasis. The human PAF receptor (PAFR) is a member of the G protein-coupled receptor (GPCR) family. Following PAF stimulation, cells become rapidly desensitized; this refractory state can be maintained for hours and is dependent on PAFR phosphorylation, internalization and trafficking. EBP50/NHERF1 has been found to interact with a variety of proteins and these interactions are involved in a growing range of functions including the assembly of signalling complexes, receptor recycling and transport of proteins to the cell surface. Crucial roles of EBP50 in GPCR physiology include its involvement in internalization, recycling, and downregulation. We were interested in identifying the role of EBP50 in PAFR trafficking. Our results showed that EBP50 binds the PAFR in its basal state, while stimulation decreased the ratio of interaction between the two proteins. We also demonstrated that EBP50 could bind PAFR via its PDZ 2 domain. In addition, we studied the role of EBP50 in various functions of the PAFR such as PAF-induced inositol phosphate accumulation and receptor internalization: EBP50 decreased the WT PAFR response and rescued the function of internalization-deficient mutant receptors, as previously described for the arrestins and the GRKs. These results suggest new roles for EBP50, some of which could help understanding the complex formation after receptor activation.
doi:10.1007/s12079-012-0175-1
PMCID: PMC3497898  PMID: 22878922
Arrestin; EBP50/NHERF1; GPCR; GRK; Internalization; PAFR
20.  Development and Utilisation of a Real-Time Display of Logged in Radiology Information System Users 
Journal of Digital Imaging  2010;24(2):295-299.
In radiology departments with multiple geographically separated reporting areas, locating radiologists can be challenging. We have developed an in-house solution to minimise the time spent looking for radiologists utilising near real-time data stored with our radiology information system (RIS). An auto updating Extensible Markup Language (XML) data feed from our RIS provider provides information about users logged into the RIS. It includes user names, their contact details and specialty interests, their location within the department, and a time stamp of last recorded dictation or report verification. The information is then displayed on our internal intranet and on a self-refreshing screen in our main department corridor. In order to estimate time savings made through the tools creation, usage statistics were calculated and combined with assessments of time taken to find a named radiologist prior to the tools implementation. Over the month of April 2009, there were 2,798 hits on the locator page. Radiologists were responsible for 1,248 hits and radiology administration staff for 1,550 hits. The average time for using the tool was calculated at 5 s. Reviewing a roster and calling/paging a radiologist took on average 30 s, and a full walk around of the department took 195 s. Through utilisation of near real-time data available within our RIS system and display of these data in an accessible form, we have developed a tool that has realised savings of up to 16 h of radiologist reporting time per week.
doi:10.1007/s10278-010-9310-9
PMCID: PMC3056972  PMID: 20532945
Real-time display; radiology information system; radiologist; clinical application; communication; data mining; extensible markup language (XML); internet technology; productivity; radiology information systems (RIS); web technology
21.  A survey of Canadian general surgery residents' interest in international surgery 
Canadian Journal of Surgery  2008;51(2):125-129.
Objective
This survey of Canadian general surgery residents was designed to determine their interest level, past experiences and awareness of opportunities in the field of international surgery.
Methods
A web-based national survey in both French and English was sent to all Canadian general surgery residents. This survey comprised 24 questions regarding demographics, education, previous international experience, interest level and perceived opportunities in international surgery.
Results
A 27% response rate revealed a high level of interest in international surgery among Canadian general surgery residents but a low level of awareness of the opportunities and relevant organizations.
Conclusion
Further initiatives are needed to increase international surgery awareness and opportunities among general surgery residents.
PMCID: PMC2386328  PMID: 18377753
22.  Incoming Resident Interest in Global Health: Occasional Travel Versus A Future Career Abroad? 
Background
While there is growing interest among residents in participating in international health experiences, it is unclear whether this interest will translate into intentions to pursue a global health career. We aimed to describe overall interest in and career intentions toward global health among interns.
Methods
We administered an anonymous survey to incoming interns in all specializations during graduate medical education orientation at 3 teaching hospitals affiliated with 2 Midwestern US medical schools in June 2009. Survey domains included demographics, previous global health experiences, interest in and barriers to participating in global health experiences during residency, and plans to pursue a future global health career.
Results
Response rate was 87% (299 of 345 residents). The most commonly reported barriers to participating in global health experiences were scheduling (82%) and financial (80%) concerns. Two-thirds of interns (65%) reported they were likely to focus on global health in their future career. Of those envisioning a global health career, 77% of interns reported interest in participating in short, occasional trips in the future; and 23% of interns intended to pursue a part-time or full-time career abroad. Interns committed to a career abroad were more willing to use vacation time (73% vs. 40% of all others, respectively; P < .001) or to personally finance the trip (58% vs. 27% of all others, respectively; P  =  < .001), and were less concerned about personal safety than interns not committed (9% vs. 26% of all others, respectively; P  =  .01).
Conclusions
Although a large proportion of incoming interns report interest in global health careers, few are committed to a global health career. Medical educators could acknowledge career plans in global health when developing global health curricula.
doi:10.4300/JGME-D-10-00168.1
PMCID: PMC3179210  PMID: 22942972
23.  Functional studies on transfected cell microarray analysed by linear regression modelling 
Nucleic Acids Research  2008;36(15):e97.
Transfected cell microarray is a promising method for accelerating the functional exploration of the genome, giving information about protein function in the living cell. The microarrays consist of clusters of cells (spots) overexpressing or silencing a particular gene product. The subsequent analysis of the phenotypic consequences of such perturbations can then be detected using cell-based assays. The focus in the present study was to establish an experimental design and a robust analysis approach for fluorescence intensity data, and to address the use of replicates for studying regulation of gene expression with varying complexity and effect size. Our analysis pipeline includes measurement of fluorescence intensities, normalization strategies using negative control spots and internal control plasmids, and linear regression (ANOVA) modelling for estimating biological effects and calculating P-values for comparisons of interests. Our results show the potential of transfected cell microarrays in studying complex regulation of gene expression by enabling measurement of biological responses in cells with overexpression and downregulation of specific gene products, combined with the possibility of assaying the effects of external stimuli. Simulation experiments show that transfected cell microarrays can be used to reliably detect even quantitatively minor biological effects by including several technical and experimental replicates.
doi:10.1093/nar/gkn428
PMCID: PMC2528170  PMID: 18628295
24.  Development and initial testing of a computer-based patient decision aid to promote colorectal cancer screening for primary care practice 
Background
Although colorectal cancer screening is recommended by major policy-making organizations, rates of screening remain low. Our aim was to develop a patient-directed, computer-based decision aid about colorectal cancer screening and investigate whether it could increase patient interest in screening.
Methods
We used content from evidence-based literature reviews and our previous decision aid research to develop a prototype. We performed two rounds of usability testing with representative patients to revise the content and format. The final decision aid consisted of an introductory segment, four test-specific segments, and information to allow comparison of the tests across several key parameters. We then conducted a before-after uncontrolled trial of 80 patients 50–75 years old recruited from an academic internal medicine practice.
Results
Mean viewing time was 19 minutes. The decision aid improved patients' intent to ask providers for screening from a mean score of 2.8 (1 = not at all likely to ask, 4 = very likely to ask) before viewing the decision aid to 3.2 afterwards (difference, 0.4; p < 0.0001, paired t-test). Most found the aid useful and reported that it improved their knowledge about screening. Sixty percent said they were ready to be tested, 18% needed more information, and 22% were not ready to be screened. Within 6 months of viewing, 43% of patients had completed screening tests.
Conclusion
We conclude that a computer-based decision aid can increase patient intent to be screened and increase interest in screening. Practice Implications: This decision aid can be viewed by patients prior to provider appointments to increase motivation to be screened and to help them decide about which modality to use for screening. Further work is required to integrate the decision aid with other practice change strategies to raise screening rates to target levels.
doi:10.1186/1472-6947-5-36
PMCID: PMC1318488  PMID: 16313676
25.  Constituents of SH1, a Novel Lipid-Containing Virus Infecting the Halophilic Euryarchaeon Haloarcula hispanica 
Journal of Virology  2005;79(14):9097-9107.
Recent studies have indicated that a number of bacterial and eukaryotic viruses that share a common architectural principle are related, leading to the proposal of an early common ancestor. A prediction of this model would be the discovery of similar viruses that infect archaeal hosts. Our main interest lies in icosahedral double-stranded DNA (dsDNA) viruses with an internal membrane, and we now extend our studies to include viruses infecting archaeal hosts. While the number of sequenced archaeal viruses is increasing, very little sequence similarity has been detected between bacterial and eukaryotic viruses. In this investigation we rigorously show that SH1, an icosahedral dsDNA virus infecting Haloarcula hispanica, possesses lipid structural components that are selectively acquired from the host pool. We also determined the sequence of the 31-kb SH1 genome and positively identified genes for 11 structural proteins, with putative identification of three additional proteins. The SH1 genome is unique and, except for a few open reading frames, shows no detectable similarity to other published sequences, but the overall structure of the SH1 virion and its linear genome with inverted terminal repeats is reminiscent of lipid-containing dsDNA bacteriophages like PRD1.
doi:10.1128/JVI.79.14.9097-9107.2005
PMCID: PMC1168735  PMID: 15994804

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