Recent Publications

Éamon W Callison, Melisa Kiyamu, Francisco C Villafuerte, Tom D Brutsaert, and Daniel E Lieberman. 2022. “Comparing high versus low-altitude populations to test human adaptations for increased ventilation during sustained aerobic activity.” Sci Rep, 12, 1, Pp. 11148.Abstract
Despite aerobic activity requiring up to tenfold increases in air intake, human populations in high-altitude hypoxic environments can sustain high levels of endurance physical activity. While these populations generally have relatively larger chest and lung volumes, how thoracic motions actively increase ventilation is unknown. Here we show that rib movements, in conjunction with chest shape, contribute to ventilation by assessing how adulthood acclimatization, developmental adaptation, and population-level adaptation to high-altitude affect sustained aerobic activity. We measured tidal volume, heart rate, and rib-motion during walking and running in lowland individuals from Boston (~ 35 m) and in Quechua populations born and living at sea-level (~ 150 m) and at high altitude (> 4000 m) in Peru. We found that Quechua participants, regardless of birth or testing altitudes, increase thoracic volume 2.0-2.2 times more than lowland participants (p < 0.05). Further, Quechua individuals from hypoxic environments have deeper chests resulting in 1.3 times greater increases in thoracic ventilation compared to age-matched, sea-level Quechua (p < 0.05). Thus, increased thoracic ventilation derives from a combination of acclimatization, developmental adaptation, and population-level adaptation to aerobic demand in different oxygen environments, demonstrating that ventilatory demand due to environment and activity has helped shape the form and function of the human thorax.
Nicholas B Holowka, Stephen M Gillinov, Emmanuel Virot, and Daniel E Lieberman. 2022. “Effects of footwear cushioning on leg and longitudinal arch stiffness during running.” J Biomech, 133, Pp. 110869.Abstract
During running, humans increase leg stiffness on more compliant surfaces through an in-series spring relationship to maintain constant support mechanics. Following this notion, the compliant midsole material of standard footwear may cause individuals to increase leg stiffness while running, especially in footwear with very thick midsoles. Recently, researchers have also proposed that footwear stiffness can affect the stiffness of the foot's longitudinal arch (LA) via a similar mechanism. To test these ideas, we used 3D motion capture to record 20 participants running on a forceplate-instrumented treadmill while barefoot, and while wearing three types of sandals composed of materials ranging an order of magnitude in Young's modulus: ethylene vinyl acetate (EVA), and two varieties of polyurethane rubber (R30 and R60). We calculated leg stiffness using standard methods, and measured LA stiffness based on medial midfoot kinematics. While there was an overall significant effect of footwear on leg stiffness (P = 0.047), post-hoc tests revealed no significant differences among individual pairs of conditions, and there was no effect of footwear on LA stiffness. However, participants exhibited significantly greater LA compression when barefoot than when running in EVA (P = 0.004) or R30 (P = 0.036) sandals. These results indicate that standard footwear midsole materials are too stiff to appreciably affect leg stiffness during running, meaning that increasing midsole thickness is unlikely to cause individuals to alter their leg stiffness. However, use of footwear does cause individuals to restrict LA compression when compared to running barefoot, and further research is needed to understand why.
Frank E Marino, Benjamin E Sibson, and Daniel E Lieberman. 2022. “The evolution of human fatigue resistance.” J Comp Physiol B, 192, 3-4, Pp. 411-422.Abstract
Humans differ from African great apes in numerous respects, but the chief initial difference setting hominins on their unique evolutionary trajectory was habitual bipedalism. The two most widely supported selective forces for this adaptation are increased efficiency of locomotion and improved ability to feed in upright contexts. By 4 million years ago, hominins had evolved the ability to walk long distances but extreme selection for endurance capabilities likely occurred later in the genus Homo to help them forage, power scavenge and persistence hunt in hot, arid conditions. In this review we explore the hypothesis that to be effective long-distance walkers and especially runners, there would also have been a strong selective benefit among Homo to resist fatigue. Our hypothesis is that since fatigue is an important factor that limits the ability to perform endurance-based activities, fatigue resistance was likely an important target for selection during human evolution for improved endurance capabilities. We review the trade-offs between strength, power, and stamina in apes and Homo and discuss three biological systems that we hypothesize humans evolved adaptations for fatigue resistance: neurological, metabolic and thermoregulatory. We conclude that the evolution of endurance at the cost of strength and power likely also involved the evolution of mechanisms to resist fatigue.
Timothy M Kistner, Bente K Pedersen, and Daniel E Lieberman. 2022. “Interleukin 6 as an energy allocator in muscle tissue.” Nat Metab, 4, 2, Pp. 170-179.Abstract
Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.
David S Ludwig, Louis J Aronne, Arne Astrup, Rafael de Cabo, Lewis C Cantley, Mark I Friedman, Steven B Heymsfield, James D Johnson, Janet C King, Ronald M Krauss, Daniel E Lieberman, Gary Taubes, Jeff S Volek, Eric C Westman, Walter C Willett, William S Yancy, and Cara B Ebbeling. 2022. “Reply to A Drewnowski et al, O Devinsky, D A Booth and E L Gibson, and D J Millward.” Am J Clin Nutr, 115, 2, Pp. 595-597.
Daniel E Lieberman, Timothy M Kistner, Daniel Richard, I-Min Lee, and Aaron L Baggish. 2021. “The active grandparent hypothesis: Physical activity and the evolution of extended human healthspans and lifespans.” Proc Natl Acad Sci U S A, 118, 50.Abstract
The proximate mechanisms by which physical activity (PA) slows senescence and decreases morbidity and mortality have been extensively documented. However, we lack an ultimate, evolutionary explanation for why lifelong PA, particularly during middle and older age, promotes health. As the growing worldwide epidemic of physical inactivity accelerates the prevalence of noncommunicable diseases among aging populations, integrating evolutionary and biomedical perspectives can foster new insights into how and why lifelong PA helps preserve health and extend lifespans. Building on previous life-history research, we assess the evidence that humans were selected not just to live several decades after they cease reproducing but also to be moderately physically active during those postreproductive years. We next review the longstanding hypothesis that PA promotes health by allocating energy away from potentially harmful overinvestments in fat storage and reproductive tissues and propose the novel hypothesis that PA also stimulates energy allocation toward repair and maintenance processes. We hypothesize that selection in humans for lifelong PA, including during postreproductive years to provision offspring, promoted selection for both energy allocation pathways which synergistically slow senescence and reduce vulnerability to many forms of chronic diseases. As a result, extended human healthspans and lifespans are both a cause and an effect of habitual PA, helping explain why lack of lifelong PA in humans can increase disease risk and reduce longevity.
David S Ludwig, Louis J Aronne, Arne Astrup, Rafael de Cabo, Lewis C Cantley, Mark I Friedman, Steven B Heymsfield, James D Johnson, Janet C King, Ronald M Krauss, Daniel E Lieberman, Gary Taubes, Jeff S Volek, Eric C Westman, Walter C Willett, William S Yancy, and Cara B Ebbeling. 2021. “The carbohydrate-insulin model: a physiological perspective on the obesity pandemic.” Am J Clin Nutr.Abstract
According to a commonly held view, the obesity pandemic is caused by overconsumption of modern, highly palatable, energy-dense processed foods, exacerbated by a sedentary lifestyle. However, obesity rates remain at historic highs, despite a persistent focus on eating less and moving more, as guided by the energy balance model (EBM). This public health failure may arise from a fundamental limitation of the EBM itself. Conceptualizing obesity as a disorder of energy balance restates a principle of physics without considering the biological mechanisms that promote weight gain. An alternative paradigm, the carbohydrate-insulin model (CIM), proposes a reversal of causal direction. According to the CIM, increasing fat deposition in the body-resulting from the hormonal responses to a high-glycemic-load diet-drives positive energy balance. The CIM provides a conceptual framework with testable hypotheses for how various modifiable factors influence energy balance and fat storage. Rigorous research is needed to compare the validity of these 2 models, which have substantially different implications for obesity management, and to generate new models that best encompass the evidence.
Anna Warrener, Robert Tamai, and Daniel E Lieberman. 2021. “The effect of trunk flexion angle on lower limb mechanics during running.” Hum Mov Sci, 78, Pp. 102817.Abstract
Trunk flexion is an understudied biomechanical variable that potentially influences running performance and susceptibility to injury. We present and test a theoretical model relating trunk flexion angle to stride parameters, joint moments and ground reaction forces that have been implicated in repetitive stress injuries. Twenty-three participants (12 male, 11 female) ran at preferred trunk flexion and three more flexed trunk positions (moderate, intermediate and high) on a custom built Bertec™ instrumented treadmill while kinematic and kinetic data were simultaneously captured. Markers adhered to bony landmarks tracked the movement of the trunk and lower limb. Stride parameters, moments of force and ground reaction force were calculated using Visual 3D (C-Motion ©) software. From preferred to high trunk flexion, stride length decreased 6% (P < 0.001) and stride frequency increased 7% (P < 0.001). Extensor moments at the hip increased 70% (P < 0.001), but knee extensor (P < 0.001) and ankle plantarflexor moments (P < 0.001) decreased 22% and 14%, respectively. Greater trunk flexion increased rate of loading by 29% (P < 0.01) and vertical ground reaction force impact transients by 20% (P < 0.01). Trunk flexion angle during running has significant effects on stride kinematics, lower extremity joint moments and ground reaction force and should be further investigated in relation to running performance and repetitive stress injuries.
Timothy M Kistner, Katherine D Zink, Steven Worthington, and Daniel E Lieberman. 2021. “Geometric morphometric investigation of craniofacial morphological change in domesticated silver foxes.” Sci Rep, 11, 1, Pp. 2582.Abstract
To test the effects of domestication on craniofacial skeletal morphology, we used three-dimensional geometric morphometrics (GM) along with linear and endocranial measurements to compare selected (domesticated) and unselected foxes from the Russian Farm-Fox Experiment to wild foxes from the progenitor population from which the farmed foxes are derived. Contrary to previous findings, we find that domesticated and unselected foxes show minimal differences in craniofacial shape and size compared to the more substantial differences between the wild foxes and both populations of farmed foxes. GM analyses and linear measurements demonstrate that wild foxes differ from farmed foxes largely in terms of less cranial base flexion, relatively expanded cranial vaults, and increased endocranial volumes. These results challenge the assumption that the unselected population of foxes kept as part of the Russian Farm-Fox experiment are an appropriate proxy for 'wild' foxes in terms of craniofacial morphology and highlight the need to include wild populations in further studies of domestication syndrome to disentangle the phenotypic effects of multiple selection pressures. These findings also suggest that marked increases in docility cannot be reliably diagnosed from shape differences in craniofacial skeletal morphology.
Andrew K Yegian, Steven B Heymsfield, and Daniel E Lieberman. 2021. “Historical body temperature records as a population-level 'thermometer' of physical activity in the United States.” Curr Biol, 31, 20, Pp. R1375-R1376.Abstract
Over the past two centuries profound technological and social changes have reduced overall levels of physical activity (PA). However, just how much population-level PA levels have declined since the Industrial Revolution is unknown because methods for measuring PA, such as accelerometry and the doubly labeled water technique, were developed only within the last few decades. Here, we show that historical records of resting body temperature (TB) can serve as a 'thermometer' of population-level PA, enabling us to use the well-documented secular decline in TB in the US1 to approximate PA decline in the US since 1820. Using cross-sectional data relating TB to resting metabolic rate (RMR) and RMR to PA, we estimate that RMR has declined by ∼6% and moderate to vigorous PA by ∼27 minutes per day since 1820 in the US.
Nicholas B Holowka, Alexander Richards, Benjamin E Sibson, and Daniel E Lieberman. 2021. “The human foot functions like a spring of adjustable stiffness during running.” J Exp Biol, 224, Pt 1.Abstract
Like other animals, humans use their legs like springs to save energy during running. One potential contributor to leg stiffness in humans is the longitudinal arch (LA) of the foot. Studies of cadaveric feet have demonstrated that the LA can function like a spring, but it is unknown whether humans can adjust LA stiffness in coordination with more proximal joints to help control leg stiffness during running. Here, we used 3D motion capture to record 27 adult participants running on a forceplate-instrumented treadmill, and calculated LA stiffness using beam bending and midfoot kinematics models of the foot. Because changing stride frequency causes humans to adjust overall leg stiffness, we had participants run at their preferred frequency and frequencies 35% above and 20% below preferred frequency to test for similar adjustments in the LA. Regardless of which foot model we used, we found that participants increased LA quasi-stiffness significantly between low and high frequency runs, mirroring changes at the ankle, knee and leg overall. However, among foot models, we found that the model incorporating triceps surae force into bending force on the foot produced unrealistically high LA work estimates, leading us to discourage this modeling approach. Additionally, we found that there was not a consistent correlation between LA height and quasi-stiffness values among the participants, indicating that static LA height measurements are not good predictors of dynamic function. Overall, our findings support the hypothesis that humans dynamically adjust LA stiffness during running in concert with other structures of the leg.
Andrew K Yegian, Yanish Tucker, Dennis M Bramble, and Daniel E Lieberman. 2021. “Neuromechanical linkage between the head and forearm during running.” Am J Phys Anthropol, 174, 4, Pp. 752-762.Abstract
OBJECTIVES: The main objective was to test the hypothesis of a neuromechanical link in humans between the head and forearm during running mediated by the biceps brachii and superior trapezius muscles. We hypothesized that this linkage helps stabilize the head and combats rapid forward pitching during running which may interfere with gaze stability. MATERIALS AND METHODS: Thirteen human participants walked and ran on a treadmill while motion capture recorded body segment kinematics and electromyographic sensors recorded muscle activation. To test perturbations to the linkage system we compared participants running normally as well as with added mass to the face and the hand. RESULTS: The results confirm the presence of a neuromechanical linkage between the head and forearm mediated by the biceps and superior trapezius during running but not during walking. In running, the biceps and superior trapezius activations were temporally linked during the stride cycle, and adding mass to either the head or hand increased activation in both muscles, consistent with our hypothesis. During walking the forces acting on the body segments and muscle activation levels were much smaller than during running, indicating no need for a linkage to keep the head and gaze stable. DISCUSSION: The results suggest that the evolution of long distance running in early Homo may have favored selection for reduced rotational inertia of both the head and forearm through synergistic muscle activation, contributing to the transition from australopith head and forelimb morphology to the more human-like form of Homo erectus. Selective pressures from the evolution of bipedal walking were likely much smaller, but may explain in part the intermediate form of the australopith scapula between that of extant apes and humans.
Jan Wilke, Lisa Mohr, Adam S Tenforde, Pascal Edouard, Chiara Fossati, Marcela González-Gross, Celso Sánchez Ramírez, Fernando Laiño, Benedict Tan, Julian David Pillay, Fabio Pigozzi, David Jimenez-Pavon, Bernhard Novak, Johannes Jaunig, Mandy Zhang, Mireille van Poppel, Christoph Heidt, Steffen Willwacher, Gustavo Yuki, Daniel E Lieberman, Lutz Vogt, Evert Verhagen, Luiz Hespanhol, and Karsten Hollander. 2021. “A Pandemic within the Pandemic? Physical Activity Levels Substantially Decreased in Countries Affected by COVID-19.” Int J Environ Res Public Health, 18, 5.Abstract
Governments have restricted public life during the COVID-19 pandemic, inter alia closing sports facilities and gyms. As regular exercise is essential for health, this study examined the effect of pandemic-related confinements on physical activity (PA) levels. A multinational survey was performed in 14 countries. Times spent in moderate-to-vigorous physical activity (MVPA) as well as in vigorous physical activity only (VPA) were assessed using the Nordic Physical Activity Questionnaire (short form). Data were obtained for leisure and occupational PA pre- and during restrictions. Compliance with PA guidelines was calculated based on the recommendations of the World Health Organization (WHO). In total, n = 13,503 respondents (39 ± 15 years, 59% females) were surveyed. Compared to pre-restrictions, overall self-reported PA declined by 41% (MVPA) and 42.2% (VPA). Reductions were higher for occupational vs. leisure time, young and old vs. middle-aged persons, previously more active vs. less active individuals, but similar between men and women. Compared to pre-pandemic, compliance with WHO guidelines decreased from 80.9% (95% CI: 80.3-81.7) to 62.5% (95% CI: 61.6-63.3). Results suggest PA levels have substantially decreased globally during the COVID-19 pandemic. Key stakeholders should consider strategies to mitigate loss in PA in order to preserve health during the pandemic.
Andrew K Yegian, Yanish Tucker, Stephen Gillinov, and Daniel E Lieberman. 2021. “Shorter distal forelimbs benefit bipedal walking and running mechanics: Implications for hominin forelimb evolution.” Am J Phys Anthropol, 175, 3, Pp. 589-598.Abstract
OBJECTIVES: Brachial index is a skeletal ratio that describes the relative length of the distal forelimb. Over the course of hominin evolution, a shift toward smaller brachial indices occurred. First, Pleistocene australopiths yield values between extant chimpanzees and humans, with further evolution in Pliocene Homo to the modern human range. We hypothesized that shorter distal forelimbs benefit walking and running performance, notably elbow and shoulder joint torques, and predicted that the benefit would be greater in running compared to walking. MATERIALS AND METHODS: We tested our hypothesis in a modern human sample walking and running while carrying hand weights, which increase the inertia (mass and effective length) of the distal forelimb, simulating a larger brachial index. RESULTS: We found longer distal forelimbs and the added mass increased elbow muscle torque by 98% while walking and 70% in running, confirming our hypothesis that shorter distal forelimbs benefit walking and running performance. Shoulder muscle torque similarly increased in both gaits with the addition of hand weights due to elongation of the effective forelimb length. Normalized elbow torque, which accounted for the effect on shoulder torque caused by the experimental manipulation, increased by 16% while walking but 52% while running, indicating that shorter distal forelimbs provide a greater benefit for running by approximately three-fold. DISCUSSION: Selection for economical bipedal walking in Australopithecus and endurance running in Homo likely contributed to the shift toward relatively smaller distal forelimbs across hominin evolution, with modern human proportions attained in Pleistocene Homo erectus and retained in later species.
Irene S Davis, Karsten Hollander, Daniel E Lieberman, Sarah T Ridge, Isabel CN Sacco, and Scott C Wearing. 2021. “Stepping Back to Minimal Footwear: Applications Across the Lifespan.” Exerc Sport Sci Rev, 49, 4, Pp. 228-243.Abstract
Minimal footwear has existed for tens of thousands of years and was originally designed to protect the sole of the foot. Over the past 50 yr, most footwear has become increasingly more cushioned and supportive. Here, we review evidence that minimal shoes are a better match to our feet, which may result in a lower risk of musculoskeletal injury.
Christopher S MacDonald, Mathias Ried-Larsen, Jalal Soleimani, Mouaz Alsawas, Daniel E Lieberman, Abdalla S Ismail, Laura P Serafim, Ting Yang, Larry Prokop, Michael Joyner, Mohammad Hassan Murad, and Amelia Barwise. 2021. “A systematic review of adherence to physical activity interventions in individuals with type 2 diabetes.” Diabetes Metab Res Rev, Pp. e3444.Abstract
Lifestyle interventions are pivotal for successful management of type 2 diabetes (T2D), however, the proportion of people with T2D adhering to physical activity advice has not been thoroughly studied. The purpose of this systematic review was to summarise the evidence on adherence to exercise or physical activity components in lifestyle interventions in those with T2D. We searched MEDLINE EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus on 12 November 2019. Eligible studies enrolled adults with T2D and reported the proportion of adherence to lifestyle interventions as a primary or secondary outcome. We included 11 studies (nine randomised controlled trials (RCTs) enrolling 1717 patients and two nonrandomised studies enrolling 62 patients). Only one of the studies had low risk of bias. The proportion of participants adhering to physical activity varied from 32% to 100% with a median of 58%. Adherence was higher in interventions using supervised training and lowest in interventions using remote coaching and the adherence rate in observational studies was higher compared to RCTs (92% vs. 55%; p < 0.01). Study duration, risk of bias, or participants' sex, were not associated with adherence to physical activity. The proportion of those with T2D adhering to physical activity interventions for T2D varies widely and most of the included studies had a high risk of bias. These findings have important implications for planning and power analysis of future trials and when counselling patients about lifestyle interventions including physical activity or exercise components.
Benjamin E Sibson, Victoria A Tobolsky, Timothy M Kistner, Nicholas B Holowka, Josphine Jemutai, Timothy K Sigei, Robert Ojiambo, Paul Okutoyi, and Daniel E Lieberman. 2021. “Trunk muscle endurance, strength and flexibility in rural subsistence farmers and urban industrialized adults in western Kenya.” Am J Hum Biol.Abstract
OBJECTIVES: High trunk muscle endurance, strength, and moderate flexibility reportedly help maintain musculoskeletal health, but there is evidence for tradeoffs among these variables as well as sex differences in trunk muscle endurance and strength. To test if these observations extend similarly to both men and women in nonindustrial and industrial environments, we investigated intra-individual associations and group and sex differences in trunk muscle endurance, strength, and flexibility among 74 (35 F, 39 M; age range: 18-61 years) adults from the same Kalenjin-speaking population in western Kenya. We specifically compared men and women from an urban community with professions that do not involve manual labor with rural subsistence farmers, including women who frequently carry heavy loads. METHODS: Trunk muscle endurance, strength, and flexibility were measured with exercise tests and electromyography (EMG). RESULTS: We found a positive correlation between trunk extensor strength and endurance (R = .271, p ≤ .05) and no associations between strength or endurance and flexibility. Rural women had higher trunk extensor and flexor endurance, EMG-determined longissimus lumborum endurance, and trunk extensor strength than urban women (all p ≤ .05). Rural women had higher trunk extensor and flexor endurance than rural men (both p ≤ .05). Urban women had lower trunk flexor and extensor endurance than urban men (both p ≤ .01). CONCLUSIONS: High levels of physical activity among nonindustrial subsistence farmers, particularly head carrying among women, appear to be associated with high trunk muscle endurance and strength, which may have important benefits for helping maintain musculoskeletal health.
Nicholas B Holowka, Ian J Wallace, Alexander Mathiessen, Robert Mang'eni Ojiambo, Paul Okutoyi, Steven Worthington, and Daniel E Lieberman. 2021. “Urbanization and Knee Cartilage Growth Among Children and Adolescents in Western Kenya.” ACR Open Rheumatol.Abstract
OBJECTIVE: Previous studies have demonstrated that low physical activity levels during youth are associated with the development of thin knee cartilage, which may increase susceptibility to osteoarthritis later in life. Here, we propose and test the hypothesis that reductions in physical activity impair knee cartilage growth among people in developing countries experiencing urbanization and increased market integration. METHODS: Ultrasonography was used to measure knee cartilage thickness in 168 children and adolescents (aged 8-17 years) from two groups in western Kenya: a rural, physically active group from a small-scale farming community and an urban, less physically active group from the nearby city of Eldoret. We used general linear models to assess the relative effects of age on cartilage thickness in these two groups, controlling for sex and leg length. RESULTS: Both groups exhibited significant reductions in knee cartilage thickness with increasing age (P < 0.0001; 95% confidence interval [CI] 0.15-0.06 mm), yet the rate of reduction was significantly less in the rural than in the urban group (P = 0.012; 95% CI 0.01-0.10 mm). CONCLUSION: The results support our hypothesis by showing that individuals from the more physically active rural group exhibited less knee cartilage loss during youth than the more sedentary urban group. Our findings suggest that reduced physical activity associated with urbanization in developing nations may affect adult knee cartilage thickness and thus could be a factor that increases susceptibility to osteoarthritis.
P Iversen. 1997. “Combined androgen blockade in the treatment of advanced prostate cancer--an overview. The Scandinavian Prostatic Cancer Group.” Scand J Urol Nephrol, 31, 3, Pp. 249-54.Abstract
The value of combined androgen blockade in the treatment of patients with advanced prostate cancer is still controversial. In this review by the Scandinavian Prostatic Cancer Group, the literature addressing the concept and its clinical use is critically reviewed.
P Strata. 1997. “Italian grants.” Nature, 385, 6612, Pp. 110.