Reconsidering low-dose aspirin therapy for cardiovascular disease: a study protocol for physician and patient behavioral change

Background

Opinion leaders represent one way to disseminate new knowledge and influence the practice behaviors of physicians. This study explored the stability of opinion leaders over time, whether opinion leaders were polymorphic (i.e., influencing multiple practice areas) or monomorphic (i.e., influencing one practice area), and reach of opinion leaders in their local network.

Methods

We surveyed surgeons and pathologists in Ontario to identify opinion leaders for colorectal cancer in 2003 and 2005 and to identify opinion leaders for breast cancer in 2005. We explored whether opinion leaders for colorectal cancer identified in 2003 were re-identified in 2005. We examined whether opinion leaders were considered polymorphic (nominated in 2005 as opinion leaders for both colorectal and breast cancer) or monomorphic (nominated in 2005 for only one condition). Social-network mapping was used to identify the number of local colleagues identifying opinion leaders.

Results

Response rates for surgeons were 41% (2003) and 40% (2005); response rates for pathologists were 42% (2003) and 37% (2005). Four (25%) of the surgical opinion leaders identified in 2003 for colorectal cancer were re-identified in 2005. No pathology opinion leaders for colorectal cancer were identified in both 2003 and 2005. Only 29% of surgical opinion leaders and 17% of pathology opinion leaders identified in the 2005 survey were considered influential for both colorectal cancer and breast cancer. Social-network mapping revealed that only a limited number of general surgeons (12%) or pathologists (7%) were connected to the social networks of identified opinion leaders.

Conclusions

Opinion leaders identified in this study were not stable over a two-year time period and generally appear to be monomorphic, with clearly demarcated areas of expertise and limited spheres of influence. These findings may limit the practicability of routinely using opinion leaders to influence practice.     

Determinants for binding of a 40 kDa protein to the leaders of yeast mitochondrial mRNAs.

An abundant yeast mitochondrial 40 kDa protein (p40) binds with high specificity to the 5'-untranslated region of cytochrome c oxidase subunit II (COX2) mRNA. Using mobility shift and competition assays, we show here that purified p40 complexes with the leaders of all eight mitochondrial mRNAs of Saccharomyces cerevisiae. The location of the protein binding site on the different leaders is not conserved with respect to the AUG start codon. In vitro RNA footprint and deletion experiments have been used to define the p40-binding site on the leaders of COX1 and ATP9 mRNAs. Nucleotides at, and near, a single stranded region are protected or exposed for DEPC modification by binding of p40 to these leaders. Removal of this region from the COX1 messenger shows that it is essential for the protein-RNA interaction. While no obvious sequence similarity can be detected between the single stranded regions in different leaders, a nearby helical segment is conserved. A consensus model for p40-RNA interactions is presented and the possible biological function of p40 is discussed.     

Leaders benefit followers in the collective movement of a social sawfly

The challenges of maintaining cohesion while making collective decisions in social or aggregating insects can result in the emergence of a leader or leaders. Larval aggregations of the steel-blue sawfly Perga affinis forage nocturnally, and some larvae lead the aggregation on foraging trips more often than expected by chance. We investigated the relationship between these leader and follower roles by comparing the weight and growth of individual larvae with different roles. Our observations reveal no significant difference between the growth of leaders and followers, suggesting that the role of leadership may not provide direct foraging benefits. However, by experimentally manipulating the social structure of larval aggregations, we found that individuals within aggregations that comprise a mixture of leaders and followers enjoy higher growth rates than those in aggregations comprising a single behavioural type. These data demonstrate, for the first time, individual benefits to maintaining a balance of leader and follower roles within larval aggregations, and highlight the importance of considering the perspectives of both leaders and followers when investigating the evolutionary significance of this behavioural variation within animal groups.     

Long 5' leaders inhibit removal of a 3' trailer from a precursor tRNA by mammalian tRNA 3' processing endoribonuclease.

Mammalian tRNA 3' processing endoribonuclease (3' tRNase) can remove a 3' trailer from various pre-tRNAs without 5' leader nucleotides. To examine how 5[prime] leader sequences affect 3' processing efficiency, we performed in vitro 3' processing reactions with purified pig 3' tRNase and pre-tRNAArgs containing a 13-nt 3' trailer and a 5[prime] leader of various lengths. The 3' processing was slightly stimulated by 5[prime] leaders containing up to 7 nt, whereas leaders of 9 nt or longer severely inhibited the reaction. Structure probing indicated that the 5' leader sequences had little effect on pre-tRNA folding. Similar results were obtained using pre-tRNA(Val)s containing a 5' leader of various lengths. We also investigated whether 3'tRNase can remove 3' trailers that are stably base-paired with 5' leaders to form an extended acceptor stem. Even such small 5' leaders as 3 and 6 nt, when base-paired with a 3' trailer, severely hindered removal of the 3' trailer by 3' tRNase.     

How does a gymnosperm branch (Pseudotsuga menziesii) assume the hydraulic status of a main stem when it takes over as leader?

In most gymnosperms, resistance to the flow of water per unit path length through the main stem is less than that of lateral branches. Using branches, leaders, and branches that have replaced missing leaders ('branch-leaders'), we tested the hypothesis that branch-leaders are at a hydraulic disadvantage. Reduced xylem transport efficiency in branch-leaders relative to leaders could be expected both because of an initial disparity in hydraulic capacity, and because of the relatively impermeable compression wood formed in branch-leaders during shoot reorientation. By subsampling branch-leaders, we also tested the hypothesis that opposite wood (formed directly opposite compression wood) is more permeable than normal wood, and could, therefore, compensate for the presence of compression wood at the whole shoot level. Fifteen months after leader removal, branch-leaders were intermediate between branches and leaders in their ability to supply foliage with water, suggesting a transition towards leader status that was not yet complete. Increased hydraulic capacity in branch-leaders was the result of increased xylem cross-sectional area per unit foliage, rather than an increase in permeability. Among subsampled wood types from basal branch-leader segments, opposite wood was significantly less permeable than normal wood, suggesting that it does not compensate for the presence of compression wood.     

Alteration of a mitochondrial tRNA precursor 5' leader abolishes its cleavage by yeast mitochondrial RNase P.

A mitochondrial specific RNase P is required to process 5' leaders from mitochondrial tRNA precursors in Saccharomyces cerevisiae. Experiments with a pair of mitochondrial pretRNAs(Asp) having leaders of different base composition suggest that this enzyme is unexpectedly sensitive to leader sequence or structure. Asp-AU (75% AU leader) is cleaved by the mitochondrial RNase P while Asp-GC (39% AU) is not. Both are substrates for E. coli RNase P. Partial nuclease digestions show that the tRNA portions of the two precursors differ in tertiary structure, while their 5' leaders differ in secondary structure. It is unusual for an RNaseP to have substrate specificity requirements which preclude processing of a pretRNA known to be a suitable substrate for an RNaseP from another species.     

ARC-1, a sequence element complementary to an internal 18S rRNA segment, enhances translation efficiency in plants when present in the leader or intercistronic region of mRNAs

The sequences of different plant viral leaders with known translation enhancer ability show partial complementarity to the central region of 18S rRNA. Such complementarity might serve as a means to attract 40S ribosomal subunits and explain in part the translation-enhancing property of these sequences. To verify this notion, we designed β-glucuronidase (GUS) mRNAs differing only in the nature of 10 nt inserts in the center of their 41 base leaders. These were complementary to consecutive domains of plant 18S rRNA. Sucrose gradient analysis revealed that leaders with inserts complementary to regions 1105–1114 and 1115–1124 (‘ARC-1’) of plant 18S rRNA bound most efficiently to the 40S ribosomal subunit after dissociation from 80S ribosomes under conditions of high ionic strength, a treatment known to remove translation initiation factors. Using wheat germ cell-free extracts, we could demonstrate that mRNAs with these leaders were translated more than three times more efficiently than a control lacking such a complementarity. Three linked copies of the insert enhanced translation of reporter mRNA to levels comparable with those directed by the natural translation enhancing leaders of tobacco mosaic virus and potato virus Y RNAs. Moreover, inserting the same leaders as intercistronic sequences in dicistronic mRNAs substantially increased translation of the second cistron, thereby revealing internal ribosome entry site activity. Thus, for plant systems, the complementary interaction between mRNA leader and the central region of 18S rRNA allows cap-independent binding of mRNA to the 43S pre-initiation complex without assistance of translation initiation factors.     

Pinus roxburghii stand dynamics at a heavily impacted site in Nepal: Research through an educational fieldweek

The fieldweek associated with the 4th Asian Dendrochronological Association Conference was an excellent opportunity for education, networking, and research. The participants and group leaders worked together for five days in an area that was new to some of the group leaders and new to some of the participants which enabled us to learn about forest ecology around Kathmandu and Nagarkot, Nepal. The fieldweek was an excellent networking opportunity and the group leaders and participants bonded which strengthened international research in dendrochronology and continues to foster new research collaborations. All of the group leaders and participants had the opportunity to learn about tree-ring formation in Pinus roxburghii at 1500 masl elevation, to explore its wood anatomy, and to examine specific research questions in our field area. In the end we developed a better understanding of the stand-age structure of a stand of trees in Nagarkot, explored the erosion history from exposed roots, and investigated tree health issues on closely related sites. We found that P. roxburghii poses some dating issues with false and micro rings at this elevation, but we were still able to develop a tree-ring chronology from this species and make preliminary assessments of stand dynamics and health.     

Sounds like a winner: voice pitch influences perception of leadership capacity in both men and women

It is well known that non-human animals respond to information encoded in vocal signals, and the same can be said of humans. Specifically, human voice pitch affects how speakers are perceived. As such, does voice pitch affect how we perceive and select our leaders? To answer this question, we recorded men and women saying ‘I urge you to vote for me this November’. Each recording was manipulated digitally to yield a higher- and lower-pitched version of the original. We then asked men and women to vote for either the lower- or higher-pitched version of each voice. Our results show that both men and women select male and female leaders with lower voices. These findings suggest that men and women with lower-pitched voices may be more successful in obtaining positions of leadership. This might also suggest that because women, on average, have higher-pitched voices than men, voice pitch could be a factor that contributes to fewer women holding leadership roles than men. Additionally, while people are free to choose their leaders, these results clearly demonstrate that these choices cannot be understood in isolation from biological influences.     

Roma political agency and spaces of social inclusion and exclusion: the contradictions of Roma self-governance amidst the rise of Hungary’s radical right

This paper examines the perspectives of local Roma leaders regarding the ongoing impacts, contradictions and civic outcomes of Hungary’s 1993 Act 77 on the Rights of National and Ethnic Minorities, legislation that created the framework for minority self-governance among Hungary’s thirteen recognized minority groups. We use interview data with Roma self-government leaders to examine the perceptions and experiences of Roma leaders regarding nationality self-governance as, alternately, a mechanism for enhancing social inclusion and political agency and/or, an institution that only exacerbates the exact exclusions it purports to address. We find that while some Roma nationality self-government leaders have been able to assert political agency and use local nationality self-governments for local initiatives, they report marked limitations in the scope of what they are able to do. This is accentuated in places marked by ethnic conflict where leaders struggle with balancing political agency against political cooptation.     

Effects of social facilitation for locating feeding sites by cattle in an eight-arm radial maze

A study was conducted in an eight-arm radial maze to determine if cattle with various foraging experiences could facilitate location of feeding sites by other cattle. Heifers assigned as "followers" (n=24) were initially trained to expect straw at the end of each arm. Initial training of heifers assigned as "leaders" (n=12) differed based on the three following treatments:(1) no-experience, (2) barley in the same two arms, and (3) barley in two arms but locations changed daily. During training, leaders with barley in fixed locations foraged more efficiently by traveling to fewer (P<0.05) arm ends to find barley than leaders in the variable treatment. After training, two followers were placed in the maze with a leader, and barley was available in two arms. Leaders facilitated the location of barley by followers. In 61% of the occasions that followers first found barley, leaders were at the feeding site. Eighty-one percent of followers later located barley without leaders in the maze. Followers with experienced leaders did not find barley consistently more often than heifers with inexperienced leaders. Cattle can apparently learn feeding site locations from other animals, but additional research is needed to evaluate the behavioral mechanisms that influence social facilitation during foraging.     

Synthetic Leaders with Potential BiP Binding Mediate High-Yield Secretion of Correctly Folded Insulin Precursors fromSaccharomyces cerevisiae

Secretion leaders are essential for expression of many heterologous proteins including insulin in yeast. The function of secretion leaders and their interaction with the secretory pathway is not clear. To determine what constitutes functional pre-pro-leader sequences inSaccharomyces cerevisiae,synthetic leader sequences for secretion of the insulin precursor were developed by a combination of rational design and stepwise systematic optimization. The synthetic leaders efficiently facilitate secretion of the insulin precursor fromS. cerevisiaewhen compared with the α-factor leader, leading to a high yield of correctly folded insulin precursor in the culture supernatant. The synthetic leaders feature two potential N-linked glycosylation sites which are efficiently glycosylated during secretion. Pulse–chase analysis indicates that the synthetic leaders/insulin precursor fusion protein have a prolonged residence in the endoplasmic reticulum compared to the α-factor leader/insulin precursor fusion protein. The longer transition time in the endoplasmic reticulum mediated by the synthetic leaders might provide additional time for correct folding of the insulin precursor and account for the increased fermentation yield.     

Expression of a micro-protein.

The smallest known open reading frame encodes the ribosomal protein L41, which in yeast is composed of only 24 amino acids, 17 of which are arginine or lysine. Because of the unique problems that might attend the translation of such a short open reading frame, we have investigated the properties and the translation of the mRNAs encoding L41. In Saccharomyces cerevisiae L41 is encoded by two linked genes, RPL41A and RPL41B. These genes give rise to mRNAs that have short 5' leaders of 18 and 22 nucleotides and rather long 3' leaders of 203 and 210 nucleotides not including their poly(A) tails. The mRNAs are translated exclusively on monosomes, suggesting that ribosomes do not remain attached to the mRNA after termination of translation. Calculations based on the abundance of ribosomes and of L41 mRNA indicate that the entire translation event, from initiation through termination, must occur in approximately 2 s. Termination of translation after only 25 codons does not subject the mRNAs encoding L41 to nonsense-mediated decay. Surprisingly, despite the L41 ribosomal protein being conserved from the archaea through the mammalia, S. cerevisiae can grow relatively normally after deletion of both RPL41A and RPL41B.     

PEROXIDASE DISTRIBUTION IN THE LEADERS OF ERECT AND INCLINED PINUS STROBUS SEEDLINGS

Westing , A. H. (Purdue U., Lafayette, Indiana.) Peroxidase distribution in the leaders of erect and inclined Pinus strobus seedlings. Amer. Jour. Bot. 47(8) : 609–612. 1960.—A longitudinal gradient of peroxidase activity, decreasing basipetally, which was independent of stem inclination, was found in the leaders of Pinus strobus L. Inclination of intact leaders also had no effect on the transverse distribution of peroxidase activity, but when such leaders were decapitated and defoliated a transverse gradient, increasing from upper side to lower, did develop. Applications of α-naphthaleneacetic acid prevented this transverse redistribution from occurring. Mutilation also resulted in an increase of the overall level of peroxidase activity in the leaders.     

Universal and variable leadership dimensions across human societies

Many researchers have turned to evolutionary theory to better understand diversity in leadership. Evolutionary theories of leadership, in turn, draw on ethnographic cases of societies thought to more closely resemble the smaller-scale, face-to-face communities in which humans evolved. Currently, though, there is limited systematic data on the nature of leadership in such societies.We coded 109 dimensions of leadership, including costs and benefits relevant to evolutionary models, in 1212 ethnographic texts from 59 mostly nonindustrial populations in Human Relations Area Files (HRAF). We discovered evidence for both cultural universals in leadership, as well as important variation by continental region, subsistence strategy, group context, and leader sex. Candidate universals included that leaders were intelligent and knowledgeable, resolved conflicts, and received material and social benefits. Evidence for other leader dimensions varied by group context (e.g., there was more evidence that leaders of kin groups were older and tended to provide counsel and direction), subsistence (e.g., hunter-gatherers tended to lack leaders with coercive authority), and sex (e.g., female leaders tended to be associated with family contexts). There was generally more evidence of benefits than costs for both leaders and followers, with material, social, and mating benefits being particularly important for leaders, and material and other benefits important for followers.Shamans emerged as an important category of leaders who did not clearly conform to influential models that emphasize two leader strategies: using knowledge and expertise to provide benefits to followers vs. using physical formidability to impose costs. Instead, shamans and other leaders with supernatural abilities used their knowledge to both provide benefits and impose costs on others. We therefore propose a modified scheme in which leaders deploy their cognitive, social, material, and somatic capital to provide benefits and/or impose costs on others.     

Perceptions of men on role of religious leaders in reproductive health issues in rural Pakistan

Religion holds unique importance in people's lives, and has been cited as an important factor in reproductive health. Pakistan has a Muslim majority and the character of the country is strongly marked by Islam. In rural areas, where the majority of the population reside, religious leaders are considered as opinion makers. The perception of adult males regarding the influence of the 'religious factor' in their use of modern contraceptive methods, and their views on the role of religious leaders in community education, were explored through a cross-sectional survey conducted in twelve rural districts of Pakistan in 2000. A sample of 180 married adult males participated in the study through consecutive sampling. The study was qualitative, utilizing tools such as in-depth and key-informant interviews. The majority of men interviewed considered that religious leaders were against fertility control, and 29% cited religion as a reason for their non-use of modern contraceptives. Respondents also suggested that the involvement of religious leaders in reproductive health programmes is essential for the programmes' effectiveness in rural areas. They thought that religious leaders could contribute positively to community education, and suggested ways in which they could educate the community in reproductive health issues. They also suggested various channels through which religious leaders could be approached to convince them to cooperate in reproductive health programmes. The study concludes that involving religious leaders in rural settings could enable reproductive health programmes and services to reach more conservative groups in society, and thus contribute effectively to bringing about positive change in the attitudes of Pakistani society towards reproductive health.     

Proximity of the start codon to a leaderless mRNA's 5' terminus is a strong positive determinant of ribosome binding and expression in Escherichia coli

An AUG start codon is an important determinant of ribosome binding and expression of leaderless mRNAs in Escherichia coli. Using reporter constructs encoding mRNAs where the AUG start codon is preceded by untranslated leaders of various length and sequence, we find that close proximity of the start codon to the 5' terminus and the leader sequence are strong determinants of both ribosome binding and expression.     

Nucleotide sequence analysis of the leader segments in a cloned copy of adenovirus 2 fiber mRNA.

Fiber mRNA of adenovirus 2 has been used as a template for RNA-dependent DNA polymerase. The resulting cDNA/RNA hybrids have been inserted at the Pst I site of the plasmid vector pBR322 after A:T tailing. One recombinant plasmid, pJAW 43, has been characterized in detail and shown to contain sequences from the main body of fiber mRNA, the three leaders common to most late adenoviral mRNAs and a fourth leader found in some species of fiber mRNA. The complete DNA sequence of the leader region has been determined and does not contain the initiation codon AUG, although this codon does occur immediately downstream from the junction between the fourth leader and the main body of the fiber mRNA. The first leader (map coordinate 16.6) is 41 nucleotides long, the second (from 19.6) is 71 nucleotides, the third (from 26.6) is 88 nucleotides and the fourth (from 78.5) is 181 nucleotides. The location of junctions between viral leaders and intervening sequences has been determined by reference, where possible, to sequences of the adenovirus 2 genome. Although the presence of short repeated sequences at the boundaries of intervening sequences and leaders makes it impossible to locate the splice point unambiguously, all of the leader-intervening sequence junctions can be arranged to stress a common feature--the presence of the dinucleotides GT and AG at the 5' and 3' ends, respectively, of the intervening sequences. This prototype sequence, which has also been recognized at or near the splice points in other eucaryotic systems, is possibly part of a larger unit which serves as a recognition site for specific excision-ligation events that ultimately lead to the production of mature mRNAs.