Woolcock Institute of Medical Research

Sydney, Australia

Woolcock Institute of Medical Research

Sydney, Australia
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News Article | November 30, 2016
Site: www.nature.com

Generally speaking, scientists aren't known as a gregarious bunch. Many identify as bookish, introverted, perhaps even a bit awkward. Yet those with more outgoing, extroverted traits might find it easier to thrive in today's scientific culture. That's because researchers in academia and industry often have to step into the spotlight, by presenting their results at seminars and meetings and forging new relationships with colleagues, funders and, increasingly, the public. Mastering these skills is especially important for young scientists who are trying to build their reputations and advance their careers. But for many shy or introverted researchers, these tasks can feel daunting, if not downright terrifying. They can even cause some to question their place in science, says Louise Harkness, a postdoc at the Woolcock Institute of Medical Research in Sydney, Australia, who has blogged about the challenges of being an introverted scientist. “A future in academia is hard for the best scientists,” says Harkness, who studies treatments for respiratory disorders. “Let alone for quiet scientists who are too shy to put their work forward. Still, quiet scientists can compete successfully with their more loquacious counterparts by cultivating their public-speaking and networking skills, as well as by engaging in creative methods of self-promotion that fit their personalities. Researchers will need to acknowledge the political dimensions of professional science and examine their own personality traits and motivations to find approaches that work best for them. Along with the myth that all scientists are introverts, there is also a widespread perception that science operates as a pure meritocracy. Many young researchers think that they just need to do good research and the rest will follow, says Donna Dean, a retired administrator at the US National Institutes of Health and an executive consultant on leadership and talent development for the US Association of Women in Science. That's usually not the case, Dean says. “We can't just sit around and do nothing and assume that people will recognize our achievements.” Indeed, Jonathan Cheek, a personality psychologist at Wellesley College in Massachusetts, says that shy or introverted people can easily get overlooked in a culture of self-promotion. “Social communication skills, such as public speaking, are the largest predictor of career success outside of whatever the technical requirements for that career are,” he says. That may not seem fair, he admits, but it's reality. Acknowledging the importance of 'soft skills' is a good first step, Cheek says, particularly for certain types of introvert (Cheek and his colleagues recognize four different categories: social, thinking, anxious and restrained introversion). Not all introverts are shy, and some of them — all except those who are anxious introverts, according to Cheek — avoid speaking up and drawing attention to themselves simply because they don't wish to or don't find the behaviour rewarding. For those scientists, he says, it can be enough to recognize that there are tangible benefits to engaging in some form of self-promotion, even if it doesn't come naturally. For others, the barriers are greater. People who experience general shyness feel discomfort when talking to strangers or in front of crowds (Cheek also helped to develop a shyness scale). And researchers who might sometimes feel unwelcome in science because of their identity — including women, minorities and those in the lesbian, gay, bisexual, transgender and queer (LGBTQ) community — can find themselves struggling to speak out in professional settings, Dean says. She adds that such discomfort might stem from a feeling that they bear the burden of representing their entire demographic group, or because they have been conditioned to be quiet as a result of their background. Many in the scientific community agree on the need to help those researchers to amplify their voices, but in the meantime, researchers can help themselves by weighing the costs and benefits of staying quiet. “You have to think about, 'What's standing between me and my goals?',” says Cheek, who identifies as an ambivert, or someone who has both introverted and extroverted traits. If people have already invested years of their life in graduate studies, Cheek says, it's likely that they have a strong stake in continuing their scientific career and so will be willing to push past their shyness. Sometimes, it just takes finding the right motivation, says Harkness, who overcame some of her quiet tendencies while doing her PhD research at the University of Sydney on gene regulation in asthmatic muscle cells. “I came to this realization that if I don't get up there and present my results, the world is missing out on these results and my thought process,” she says (see 'Embrace your quietness'). Almost all scientists, at one point or another, have to share their research in front of crowds — a task that strikes dread into the hearts of many, not just the introverted and shy. Some surveys, such as the Chapman University Survey on American Fears conducted in 2014, show that in the United States, fear of public speaking often tops people's list of phobias, beating even fear of drowning in some cases. “Early in my PhD, I recognized it was something I was abysmal at,” says Paul Brack, a PhD student at Loughborough University, UK, who studies ways to produce hydrogen for fuel cells. “I wanted to become average — that was my aspiration.” Fortunately, Cheek says, public speaking is not as hard to learn as many people fear, and doesn't require quiet researchers to become extroverts. The main reason, he adds, that most people loathe public speaking is that they haven't done it very much, and getting better at it just takes practice. Many universities offer resources to help scientists to become comfortable presenting at meetings and to hone their speaking skills, says biochemist Kate Sleeth, interim associate dean of administration and student development at City of Hope hospital in Duarte, California. If an institution has no such offerings, Sleeth — also an introvert, who now chairs the board of directors of the National Postdoctoral Association — recommends seeking out groups such as Toastmasters International, a non-profit organization dedicated to helping its members to become better communicators. Another strategy is for researchers to develop a presentation style that feels comfortable to them. For Harkness, that involved using her talks to illustrate her thought process, rather than just to disseminate her findings. “I want to take people through the story,” she says. Stepping through the evolution of a research project actually made her feel better about presenting her work, she says. “I'm quite proud to show it.” Networking can also be adapted to individual preferences, despite the intimidating connotation that it has for many scientists. “The word 'networking' makes a lot of people feel like they are going to have to come up with some sort of beautifully flowing conversational piece,” says Brack, who wrote about the subject in a Naturejobs blogpost last year (see go.nature.com/2fx60wc). But he has devised several ways to network that suit him, as an introvert who also used to be very shy. One strategy involves approaching individuals — rather than big groups — at networking events at meetings with a question or two in mind ahead of time. If Brack strikes up a conversation with a fellow graduate student, he usually leads with questions about their research, adviser and university. You don't even have to stick to science, says Dean, who still finds networking hard. Perhaps you notice something on someone's name badge — such as being from the same place — or share a hobby or other connection. “Get people talking about themselves,” she says. Dean advises young scientists to set a goal of talking to two or three new people each time they go to a conference, and she urges them to avoid describing their work in self-deprecating terms. Sleeth also suggests taking along an outgoing friend who will help you to feel comfortable, but who will not hog the limelight. Quiet scientists might also consider collaborating with more-extroverted colleagues on research. “It makes it so much easier,” Sleeth says. Ultimately, even if these tasks don't ever feel natural to many quiet scientists, those scientists should not despair, says Steve Blank, who teaches entrepreneurship at Stanford University in California and is the architect of the US National Science Foundation's Innovation Corps Program, which helps scientists to commercialize their discoveries. “By definition, scientists are pretty smart,” Blank says. “While you might not have it in your gut, you have enough computing power to emulate it.” When making big career choices, quiet scientists might want to consider how different paths in science might suit their personality. For instance, academia probably entails teaching and giving many public talks, whereas government agencies might require more lab work and meetings with agency managers. As entrepreneurs in the tech industry, Blank says, scientists have to sell their ideas to investors and customers. “If you want a leadership role, I'd say the biggest thing you need to learn is to communicate,” he says. And that often involves at least learning to emulate an extrovert. Because of the diverse demands of different scientific trajectories, Cheek recommends that early-career scientists look at literature such as Holland's theory of vocational choice, developed by the late John Holland, a psychologist at Johns Hopkins University in Baltimore, Maryland. “It's sort of a theory about how work environments have personalities,” he says. Both people and occupations are ranked against Holland's framework, and three of the categories — realistic, investigative and artistic — are well suited to introverts. These might correspond to more applied, theoretical and creative career paths, respectively. Scientists should not let such classifications dissuade them from following their aspirations, Cheek says, but they should consider whether their personality is compatible with their intended career choice. “Your preference, when it interacts with the structure of the field, maybe doesn't make your favourite thing the most rewarded thing,” he says. Part of finding a fulfilling career is about finding a good fit. That's what Harkness has begun to realize, although she didn't formally consult Holland's theory. After her PhD, she moved to the Woolcock Institute, where research groups are smaller and more tightly knit, she says. That makes it a good place for her as a young, introverted scientist, she explains. Public speaking and in-person networking are seen as crucial to success in science and so many other fields partly because our culture tends to be geared towards extroverts. At least, that's the argument in Quiet (Broadway, 2013), a book by US writer and lecturer Susan Cain about the power of introverts. Her central argument is that society often treats introversion as a personality flaw, but that introverts should be valued. Quiet scientists can show off their strengths in a variety of ways. David Steen has had great success with social media. A wildlife ecologist at Auburn University in Alabama, he is a proud introvert. “I don't manage it — I embrace it,” he says. Steen describes himself as the guy who sits in the back of meetings and doesn't say much; similarly to many introverts, he prefers to gather his thoughts before he speaks. Then, he communicates through tools such as Twitter, where he has more than 12,800 followers (Slate magazine crowned him “best biologist on Twitter” in 2015). The medium offers him the opportunity to gain visibility and to interact with the broader scientific community at his own pace and on his terms. “Can take all day to write a tweet,” said Steen, in a tweet. “Compare that to the brief window of time you have during a meeting to come up with verbal eloquence.” Cheek recommends creating a Google Scholar profile and becoming active on ResearchGate and Academia.edu. Researchers can also use LinkedIn to advertise scientific qualifications and promote publications and awards, Brack says. “You can share that in a way that you don't feel like you are ramming it in people's faces, or being overbearing.” Shy and introverted researchers can advance their careers in other ways that feel compatible with their personalities. Brack recommends joining committees, as he did recently to help organize a chemistry conference in Scotland. “I find that I need to be around someone quite a while before I'm comfortable enough to really talk to them and make that sort of a connection,” he says. “Being in a committee is quite useful for that.” Researchers can also follow up on meetings and seminars with e-mails to contribute to and stay involved in scientific discussions, particularly if they don't want to speak up in a group setting. Regardless of the strategy that researchers choose, Sleeth recommends seeking out a mentor, or even a sponsor — whom she defines as someone who will advocate for and endorse young scientists — and especially shy and introverted ones. That person could be their adviser or it could be a co-author or colleague, she says. The important thing is that they help to open doors for young scientists and advertise their strengths and accomplishments. “Because then you're not bragging,” she says. “Someone else is doing it on your behalf.”


Ryan N.M.,University of Newcastle | Ryan N.M.,Hunter Medical Research Institute | Birring S.S.,King's College London | Gibson P.G.,University of Newcastle | And 2 more authors.
The Lancet | Year: 2012

Background: Refractory chronic cough causes substantial symptoms and quality-of-life impairment. Similarities between central reflex sensitisation in refractory chronic cough and neuropathic pain suggest that neuromodulators such as gabapentin might be effective for refractory chronic cough. We established the efficacy of gabapentin in patients with refractory chronic cough. Methods: This randomised, double-blind, placebo-controlled trial was undertaken at an outpatient clinic in Australia. Adults with refractory chronic cough (>8 weeks' duration) without active respiratory disease or infection were randomly assigned to receive gabapentin (maximum tolerable daily dose of 1800 mg) or matching placebo for 10 weeks. Block randomisation was done with randomisation generator software, stratified by sex. Patients and investigators were masked to assigned treatment. The primary endpoint was change in cough-specific quality of life (Leicester cough questionnaire [LCQ] score) from baseline to 8 weeks of treatment, analysed by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12608000248369. Findings: 62 patients were randomly assigned to gabepentin (n=32) or placebo (n=30) and ten patients withdrew before the study end. Gabapentin significantly improved cough-specific quality of life compared with placebo (between-group difference in LCQ score during treatment period 1·80, 95 CI 0·56-3·04; p=0·004; number needed to treat of 3·58). Side-effects occurred in ten patients (31) given gabapentin (the most common being nausea and fatigue) and three (10) given placebo. Interpretation: The treatment of refractory chronic cough with gabapentin is both effective and well tolerated. These positive effects suggest that central reflex sensitisation is a relevant mechanism in refractory chronic cough. Funding: National Health and Medical Research Council of Australia and Hunter Medical Research Institute, Newcastle, Australia. © 2012 Elsevier Ltd.


Buonanno G.,University of Cassino and Southern Lazio | Buonanno G.,Queensland University of Technology | Marks G.B.,Woolcock Institute of Medical Research | Morawska L.,Queensland University of Technology
Environmental Pollution | Year: 2013

Air pollution is a widespread health problem associated with respiratory symptoms. Continuous exposure monitoring was performed to estimate alveolar and tracheobronchial dose, measured as deposited surface area, for 103 children and to evaluate the long-term effects of exposure to airborne particles through spirometry, skin prick tests and measurement of exhaled nitric oxide (eNO). The mean daily alveolar deposited surface area dose received by children was 1.35 × 103 mm2. The lowest and highest particle number concentrations were found during sleeping and eating time. A significant negative association was found between changes in pulmonary function tests and individual dose estimates. Significant differences were found for asthmatics, children with allergic rhinitis and sensitive to allergens compared to healthy subjects for eNO. Variation is a child's activity over time appeared to have a strong impact on respiratory outcomes, which indicates that personal monitoring is vital for assessing the expected health effects of exposure to particles. © 2013 Elsevier Inc. All rights reserved.


McDonald V.M.,University of Newcastle | McDonald V.M.,Hunter Medical Research Institute | Higgins I.,University of Newcastle | Wood L.G.,Hunter Medical Research Institute | And 3 more authors.
Thorax | Year: 2013

Introduction The rising disease burden from chronic obstructive pulmonary disease (COPD) requires new approaches. Method We suggest an approach based around three elements: inflammometry and multidimensional assessment to identify therapeutic targets and case management to design and implement an individualised treatment programme based on these assessments. Discussion This tailored approach to treatment would maximise efficacy, limit cost and permit a better risk- benefit ratio of treatment. The advantages include the ability to add up the benefits of individual therapies leading to a cumulative therapeutic benefit that is greater than each individual therapy alone. We can now design a multifaceted inflammometry intervention for airway diseases based on targeting eosinophilic inflammation, non-eosinophilic pathways and systemic inflammation. COPD is a complex and challenging disease. The use of inflammometry and multidimensional assessment is necessary to identify relevant treatment targets and maximise the scope of therapy while limiting unnecessary use of drugs. An individualised programme of management can be designed and coordinated by using a case manager. This new approach may provide tangible benefits to people with COPD.


Beasley R.,Medical Research Institute of New Zealand | Weatherall M.,University of Otago | Shirtcliffe P.,Medical Research Institute of New Zealand | Hancox R.,University of Otago | Reddel H.K.,Woolcock Institute of Medical Research
Journal of Allergy and Clinical Immunology | Year: 2014

The recommended treatment of mild asthma is regular maintenance inhaled corticosteroids (ICSs) with a short-acting β-agonist as a separate inhaler used when needed for symptom relief. However, the benefits of regular ICS use in actual clinical practice are limited by poor adherence and low prescription rates. An alternative strategy would be the symptom-driven (as-required or "prn") use of a combination ICS/short-acting β-agonist or ICS/long-acting β-agonist inhaler as a reliever rather than regular maintenance use. The rationale for this approach is to titrate both the ICS and β-agonist dose according to need and enhance ICS use in otherwise poorly adherent patients who overrely on their reliever β-agonist inhaler. This strategy will only work if the β-agonist component has a rapid onset of action for symptom relief. There is evidence to suggest that this regimen has advantages over regular ICS therapy and might represent an effective, safe, and novel therapy for the treatment of intermittent and mild asthma. In this commentary we review this evidence and propose that randomized controlled trials investigating different combination ICS/β-agonist inhaler products prescribed according to this regimen in intermittent and mild asthma are an important priority. © 2013 American Academy of Allergy, Asthma & Immunology.


Herath S.C.,Woolcock Institute of Medical Research
The Cochrane database of systematic reviews | Year: 2013

Whether or not regular treatment of COPD patients with prophylactic antibiotics reduces exacerbations or affects quality of life. We searched the Cochrane Airways Group Trials Register and bibliographies of relevant studies. The latest literature search was August 2013. Randomised controlled trials (RCTs) that compared prophylactic antibiotics with placebo in patients with COPD. We used the standard methods of The Cochrane Collaboration. Data were extracted and analysed by two independent review authors. Seven RCTs involving 3170 patients were included in this systematic review. All studies were published between 2001 and 2011. Five studies were of continuous antibiotics and two studies were of intermittent antibiotic prophylaxis (termed 'pulsed' for this review). The antibiotics investigated were azithromycin, erythromycin, clarithromycin and moxifloxacin. Azithromycin, erythromycin and clarithromycin are macrolides while moxifloxacin is a fourth-generation synthetic fluoroquinolone antibacterial agent. The study duration varied from three months to 36 months and all used intention-to-treat analysis. Most of the results were of moderate quality. The risk of bias of the included studies was generally low, and we did not downgrade the quality of evidence for risk of bias.The trials recruited participants with a mean age of 66 years and with at least a moderate severity of COPD. Three trials included participants with frequent exacerbations and two trials recruited participants requiring systemic steroids or antibiotics, or both, or who were at the end stage of their disease and required oxygen.The primary outcomes for this review were the number of exacerbations and quality of life.With use of continuous prophylactic antibiotics the number of patients experiencing an exacerbation was reduced (odds ratio (OR) 0.55; 95% confidence interval (CI) 0.39 to 0.77, 3 studies, 1262 participants, high quality). This represented a reduction from 69% of participants in the control group compared to 54% in the treatment group (95% CI 46% to 63%) and the number needed to treat to prevent one exacerbation (NNTb) was therefore 8 (95% CI 5 to 18). The frequency of exacerbations was also reduced with continuous prophylactic antibiotic treatment (rate ratio 0.73; 95% CI 0.58 to 0.91).Use of pulsed antibiotic treatment showed a non-significant reduction in the number of people with exacerbations (OR 0.87; 95% CI 0.69 to 1.09, 1 study, 1149 participants, moderate quality) and the test for interaction showed that this result was significantly different from the effect on exacerbations with continuous antibiotics.There was a statistically significant improvement in quality of life with both continuous and pulsed antibiotic treatment but this was smaller than the four unit improvement that is regarded as being clinically significant (MD -1.78; 95% CI -2.95 to -0.61, 2 studies, 1962 participants, moderate quality).Neither pulsed nor continuous antibiotics showed a significant effect on the secondary outcomes of frequency of hospital admissions, change in lung function, serious adverse events or all-cause mortality (moderate quality evidence).The adverse events that were recorded varied among the trials depending on the different antibiotics used. Azithromycin was associated with a significant hearing loss in the treatment group. The moxifloxacin pulsed study reported a significantly higher number of adverse events in the treatment arm due to the marked increase in gastrointestinal adverse events (P < 0.001). Some adverse events that led to drug discontinuation, such as development of long QTc or tinnitus, were not significantly more frequent in the treatment group than the placebo group but pose important considerations in clinical practice.The development of antibiotic resistance in the community is of major concern. One study found newly colonised patients to have higher rates of antibiotic resistance. Patients colonised with moxifloxacin-sensitive pseudomonas at initiation of therapy rapidly became resistant with the quinolone treatment. Use of continuous prophylactic antibiotics results in a clinically significant benefit in reducing exacerbations in COPD patients. All trials of continuous antibiotics used macrolides hence the noted benefit applies only to the use of continuous macrolide antibiotics. The impact of pulsed antibiotics remains uncertain and requires further research.The trials in this review included patients who were frequent exacerbators and needed treatment with antibiotics or systemic steroids, or who were on supplemental oxygen. There were also older individuals with a mean age of 66 years. The results of these trials apply only to the group of patients who were studied in these trials and may not be generalisable to other groups.Because of concerns about antibiotic resistance and specific adverse effects, consideration of prophylactic antibiotic use should be mindful of the balance between benefits to individual patients and the potential harms to society created by antibiotic overuse.


Lee W.-H.,Woolcock Institute of Medical Research | Loo C.-Y.,Woolcock Institute of Medical Research | Traini D.,Woolcock Institute of Medical Research | Young P.M.,Woolcock Institute of Medical Research
Expert Opinion on Drug Delivery | Year: 2015

Introduction: Macrophages are the most versatile cells in the hematopoietic system and are strategically distributed in tissues to fight pathogens or other foreign particles. In the lung, however, for intracellular infections such as tuberculosis, pneumonia and aspergillosis, bacteria and fungi utilize the alveolar macrophage as a breeding ground. This has become a challenge for the treatment of these infections, as most drugs do not effectively reach the macrophages at therapeutic levels. Alveolar macrophages also play an important role to initiative adaptive immunity toward combating inflammation and cancer in the lung.Areas covered: This review focuses on the development of micro- and nanotechnology-based drug delivery systems to target alveolar macrophages in association with intracellular infections, cancer and lung inflammation. Aspects of nanoparticle and micron-sized particle engineering through exploitation of particles' physicochemical characteristics such as particle size, surface charge and geometry of particles are discussed. In addition, the application of nanocarriers such as liposomes, polymeric nanoparticles and dendrimers are covered with respect to macrophage targeting.Expert opinion: Drug delivery targeted to alveolar macrophages in the lung is becoming a reality thanks to micro- and nanotechnology breakthrough. The literature review shows that regulation of physicochemical parameters of particles could be a recipe to enhance macrophage targeting and uptake. However, there is still a need to identify more target-specific receptors in order to facilitate drug targeting. Besides that, the toxicity of nanocarriers arising from prolonged residence in the lung should be taken into consideration during formulation. © 2014 Informa UK, Ltd.


Bartlett D.J.,Woolcock Institute of Medical Research
The Medical journal of Australia | Year: 2013

Delayed sleep phase disorder (DSPD) - a circadian rhythm sleep disorder - is most commonly seen in adolescents. The differential diagnosis between DSPD and conventional psychophysiological insomnia is important for correct therapeutic intervention. Adolescent DSPD sleep duration is commonly 9 hours or more. Depression may be comorbid with DSPD. DSPD has a negative impact on adolescent academic performance. DSPD treatments include bright light therapy, chronotherapeutic regimens, and administration of melatonin as a chronobiotic (as distinct from a soporific). Attention to non-photic and extrinsic factors including healthy sleep parameters is also important to enable better sleep and mood outcomes in adolescents.


Ichimaru Y.,Woolcock Institute of Medical Research
American journal of physiology. Lung cellular and molecular physiology | Year: 2012

Chronic obstructive pulmonary disease (COPD) and asthma are characterized by irreversible remodeling of the airway walls, including thickening of the airway smooth muscle layer. Perlecan is a large, multidomain, proteoglycan that is expressed in the lungs, and in other organ systems, and has been described to have a role in cell adhesion, angiogenesis, and proliferation. This study aimed to investigate functional properties of the different perlecan domains in relation to airway smooth muscle cells (ASMC). Primary human ASMC obtained from donors with asthma (n = 13), COPD (n = 12), or other lung disease (n = 20) were stimulated in vitro with 1 ng/ml transforming growth factor-β(1) (TGF-β(1)) before perlecan deposition and cytokine release were analyzed. In some experiments, inhibitors of signaling molecules were added. Perlecan domains I-V were seeded on tissue culture plates at 10 μg/ml with 1 μg/ml collagen I as a control. ASM was incubated on top of the peptides before being analyzed for attachment, proliferation, and wound healing. TGF-β(1) upregulated deposition of perlecan by ASMC from COPD subjects only. TGF-β(1) upregulated release of IL-6 into the supernatant of ASMC from all subjects. Inhibitors of SMAD and JNK signaling molecules decreased TGF-β(1)-induced perlecan deposition by COPD ASMC. Attachment of COPD ASMC was upregulated by collagen I and perlecan domains IV and V, while perlecan domain II upregulated attachment only of asthmatic ASMC. Seeding on perlecan domains did not increase proliferation of any ASMC type. TGF-β(1)-induced perlecan deposition may enhance attachment of migrating ASMC in vivo and thus may be a mechanism for ASMC layer hypertrophy in COPD.


Reddel H.K.,Woolcock Institute of Medical Research
Clinics in Chest Medicine | Year: 2012

Control-based asthma management has been incorporated in asthma guidelines for many years. This article reviews the evidence for its utility in adults, describes its strengths and limitations in real life, and proposes areas for further research, particularly about incorporation of future risk and identification of patients for whom phenotype-guided treatment would be effective and efficient. The strengths of control-based management include its simplicity and feasibility for primary care, and its limitations include the nonspecific nature of asthma symptoms, the complex role of β2-agonist use, barriers to stepping down treatment, and the underlying assumptions about asthma pathophysiology and treatment responses. © 2012 Elsevier Inc.

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