Background Metformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age. Objectives To assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies. Search strategy A comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Selection criteria Prospective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Data collection and analysis The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data. Main results Pooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies. Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.

BackgroundMetformin is an oral anti-hyperglycemic agent that has been shown to reduce total mortality compared to other anti-hyperglycemic agents, in the treatment of type 2 diabetes mellitus. Metformin, however, is thought to increase the risk of lactic acidosis, and has been considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age.ObjectivesTo assess the incidence of fatal and nonfatal lactic acidosis, and to evaluate blood lactate levels, for those on metformin treatment compared to placebo or non-metformin therapies.Search strategyA comprehensive search was performed of electronic databases to identify studies of metformin treatment. The search was augmented by scanning references of identified articles, and by contacting principal investigators.Selection criteriaProspective trials and observational cohort studies in patients with type 2 diabetes of least one month duration were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy.Data collection and analysisThe incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for non-metformin treatments. The upper limit for the true incidence of cases was calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values (basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed-effect model for continuous data.Main resultsPooled data from 347 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 70,490 patient-years of metformin use or in 55,451 patients-years in the non-metformin group. Using Poisson statistics the upper limit for the true incidence of lactic acidosis per 100,000 patient-years was 4.3 cases in the metformin group and 5.4 cases in the non-metformin group. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to non-metformin therapies.Authors' conclusionsThere is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments.

PURPOSE The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is a need to identify more effective predictors than the traditional staging system to aid therapeutic decision-making. We performed a systematic review and meta-analysis of gene expression profiles (GEPs) to assess their utility for risk stratification and prediction of poor outcomes in stage II CRC. PATIENTS AND METHODS We performed a comprehensive literature search through December 2007. Studies were included if they reported GEP-based assays in patients with stage II CRC, and either subsequent cancer recurrence or death within 3 years. The prognostic likelihood ratio (LR) and odds ratio (OR) were calculated with 95% confidence intervals and pooled using the fixed-effects method. The weighted average sensitivity, specificity, and accuracy were also reported. RESULTS Eight cohorts involving 271 patients contributed to the analysis. The average accuracy, sensitivity, and specificity were 81.9%, 76.2%, and 84.5%, respectively, with a prognostic LR of 4.7 (95% CI, 3.2-6.8) and a prognostic OR of 15.1 (95% CI, 7.9-28.6). No evidence for significant interstudy heterogeneity was noted in either analysis. Subgroup analysis found no difference in results for the prediction of cancer recurrence or death. CONCLUSION This analysis demonstrates the promising potential of using GEP assays as predictors of poor outcomes in stage II CRC, such as cancer recurrence or death. To maximize their utility and availability, further studies will be needed to identify and validate specific gene signatures for poor prognosis in stage II CRC.

BACKGROUND:There is uncertainty over the risks and benefits of hormone therapy. We performed a Bayesian meta-analysis to evaluate the effect of hormone therapy on total mortality in younger postmenopausal women. This analysis synthesizes evidence from different sources, taking into account varying views on the issue.METHODS:A comprehensive search from 1966 through January 2008 identified randomized controlled trials of at least 6 month's duration that evaluated hormone therapy in women with mean age <60 years and reported at least one death, and prospective observational cohort studies that evaluated the relative risk of mortality associated with hormone therapy after adjustment for confounding variables.RESULTS:The results were synthesized using a hierarchical random-effects Bayesian meta-analysis. The pooled results from 19 randomized trials, with 16,000 women (mean age 55 years) followed for 83,000 patient-years, showed a mortality relative risk of 0.73 (95% credible interval 0.52-0.96). When data from 8 observational studies were added to the analysis, the resultant relative risk was 0.72 (credible interval 0.62-0.82). The posterior probability that hormone therapy reduces total mortality in younger women is almost 1.CONCLUSIONS:The synthesis of data using Bayesian meta-analysis indicates a reduction in mortality in younger postmenopausal women taking hormone therapy compared with no treatment. This finding should be interpreted taking into account the potential benefits and harms of hormone therapy.

OBJECTIVE:To assess the effect of hormone therapy (HT) on coronary heart disease (CHD) events in younger and older postmenopausal women.DESIGN:A comprehensive database search identified randomized-controlled trials of HT of at least 6 months' duration that reported CHD events, defined as myocardial infarction or cardiac death.MEASUREMENTS:The pooled odds ratios (ORs) for CHD events were reported separately for younger and older women, defined as participants with mean time from menopause of less than or greater than 10 years, or mean age less than or greater than 60 years.MAIN RESULTS:Pooled data from 23 trials, with 39,049 participants followed for 191,340 patient-years, showed that HT significantly reduced CHD events in younger women (OR 0.68 [confidence interval (C I), 0.48 to 0.96]), but not in older women (OR 1.03 [CI, 0.91 to 1.16]). Hormone therapy reduced events in younger women compared with older women (OR 0.66 [CI, 0.46 to 0.95]). In older women, HT increased events in the first year (OR 1.47 [CI, 1.12 to 1.92]), then reduced events after 2 years (OR 0.79 [CI, 0.67 to 0.93]).CONCLUSIONS:Hormone therapy reduces the risk of CHD events in younger postmenopausal women. In older women, HT increases, then decreases risk over time.

PURPOSE:To evaluate the health and economic outcomes of hormone therapy in younger and older postmenopausal women.METHODS:We developed a cost-effectiveness model to evaluate outcomes associated with hormone therapy in younger and older postmenopausal women, using data sources from published literature through March 2008. The target population was 50-year-old and 65-year-old women given hormone therapy or no therapy, and then followed over their lifetime. Primary outcomes measured were quality-adjusted life-years (QALYs) and incremental cost per QALY gained.RESULTS:For the base-case analysis, hormone therapy for 15 years in the younger cohort resulted in a gain of 1.49 QALYs with an incremental cost of $2438 per QALY gained, compared with no therapy. The results for younger women were robust to all sensitivity analyses, and treatment remained highly cost-effective (<$10,000 per QALY gained) within the range of individual assumptions used. Treatment durations of 5 years and 30 years also were highly cost-effective. In the older cohort, treatment for 15 years resulted in a net gain of 0.11 QALYs with a cost of $27,953 per QALY gained. However, a loss of QALYs was seen in the first 9 years. The results for older women were sensitive to many of the assumptions used.CONCLUSIONS:Hormone therapy for 5 to 30 years in younger postmenopausal women increases quality-adjusted life-years and is cost-effective. Hormone therapy started in later years results in a loss of quality-adjusted life for several years before a net gain can be realized.

15054 Background: The use of adjuvant therapy in stage II colorectal cancer (CRC) remains controversial. There is clearly a need to identify better predictors than the traditional staging system to aid therapeutic decisions. Gene expression profiling (GEP) has been demonstrated as a useful tool in risk stratification in many cancers. We performed a meta-analysis to assess its utility for predicting poor outcomes in stage II CRC. Methods: We performed literature searches of MEDLINE, the Cochrane Library, EMBASE, Cancerlit, and ASCO Proceedings through December 2007. Studies were included if they reported GEP-based assays in patients with stage II CRC, and either subsequent cancer recurrence or death within 3 years. The prognostic likelihood ratio (LR) (sensitivity/ 1-specificity) was obtained for each study and then pooled using the random-effects method to obtain a weighted mean LR and associated 95% confidence intervals (CI). The average accuracy, sensitivity, and specificity are also reported. Results: Eight cohorts with extractable data were identified and included in the analysis. A total of 271 patients were studied, with average follow-up time ranging from 3.0 to 5.6 years. The average accuracy, sensitivity, and specificity were 81.9%, 76.2%, and 84.5%, respectively, with a prognostic LR of 4.54 [95% CI 3.16 to 6.53]. The p value for overall effect was < 0.00001. No evidence for significant inter-study heterogeneity was noted (p = 0.94). Conclusions: This analysis demonstrates promising potential of using GEP assays as predictors of poor outcomes in stage II colorectal cancer, such as cancer recurrence or death. To maximize their utility and availability, further studies will be needed to identify and validate specific gene signatures for poor prognosis in stage II CRC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Almac Diagnostics, H. Lee Moffitt Cancer Center & Research Institute Almac Diagnostics Almac Diagnostics

PURPOSE: We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes.METHODS: We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes.RESULTS: Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (-5.3%, 95% confidence interval [CI], -6.7--4.0), fasting glucose (-4.5%, CI, -6.0--3.0), fasting insulin (-14.4%, CI, -19.9--8.9), calculated insulin resistance (-22.6%, CI, -27.3--18.0), triglycerides (-5.3%, CI, -10.5--0.03), and low-density lipoprotein cholesterol (-5.6%, CI, -8.3--3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years.CONCLUSION: Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials. (C) 2008 Elsevier Inc. All rights reserved.

I discuss especially my summer with Willy Fowler at Kellogg Radiation Laboratory in 1951, where I did my 'triple alpha' work. I also go back even earlier to Arthur Eddington and Hans Bethe. The 1953 summer school in Ann Arbor only gets a mention.

We read with interest the recent meta-analysis of metformin treatment in persons at risk for diabetes mellitus.1Salpeter S.R. Buckley N.S. Kahn J.A. Salpeter E.E. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus.Am J Med. 2008; 121: 149-157Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality of women, affecting 6.5% to 9% of unselected women, and is the most common cause of oligo-ovulatory infertility.2Knochenhauer E.S. Key T.J. Kahsar-Miller M. et al.Prevalence of the polycystic ovary syndrome in unselected black and white women of the southeastern United States: a prospective study.J Clin Endocrinol Metab. 1998; 83: 3078-3082Crossref PubMed Scopus (1526) Google Scholar Because upward of 65% of women with PCOS demonstrate insulin resistance and hyperinsulinemia, many of these women are at increased risk for developing type 2 diabetes mellitus and other metabolic complications. As Salpeter et al1Salpeter S.R. Buckley N.S. Kahn J.A. Salpeter E.E. Meta-analysis: metformin treatment in persons at risk for diabetes mellitus.Am J Med. 2008; 121: 149-157Abstract Full Text Full Text PDF PubMed Scopus (194) Google Scholar recognized, metformin has been used for several years for the treatment of PCOS, which improves many features of the syndrome, including the associated hyperandrogenism, ovulatory dysfunction, and metabolic abnormalities. With recent evidence that metformin treatment only modestly improves ovulation and pregnancy rates,3Legro R.S. Barnhart H.X. Schlaff W.D. et al.Clomiphene, metformin, or both for infertility in the polycystic ovary syndrome.N Engl J Med. 2007; 356: 551-566Crossref PubMed Scopus (796) Google Scholar the use of metformin in PCOS increasingly emphasizes its long-term metabolic benefits. Currently, many women are maintained on metformin in the hope that this will prevent the development of diabetes and cardiovascular disease; however, such benefits are proposed on the basis of extrapolations of the results of studies in other populations, namely, the Diabetes Prevention Program and the United Kingdom Prospective Diabetes Study, respectively.4UK Prospective Diabetes Study (UKPDS) GroupEffect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34).Lancet. 1998; 352: 854-865Abstract Full Text Full Text PDF PubMed Scopus (7545) Google Scholar, 5Knowler W.C. Barrett-Connor E. Fowler S.E. et al.Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403Crossref PubMed Scopus (14793) Google Scholar The meta-analysis by Salpeter et al included many studies in PCOS cohorts, and we wondered whether subjects with PCOS in these studies demonstrated a similar improvement in metabolic parameters and the development rate of diabetes and other metabolic morbidities while receiving metformin, as did individuals without PCOS. These data would be useful for the care and counseling of patients with this prevalent and morbid syndrome. The ReplyThe American Journal of MedicineVol. 121Issue 8PreviewWe appreciate the thoughtful comments by Goodarzi and Azziz concerning the results of our meta-analysis on metformin treatment in individuals at risk for diabetes mellitus.1 We evaluated the metabolic effects of metformin treatment in subjects with and without known polycystic ovary syndrome (PCOS) who were at risk for diabetes. We report beneficial effects of metformin treatment on body mass index, fasting glucose, fasting insulin, calculated insulin resistance, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and the incidence of new-onset diabetes, with no significant difference in results seen for those with and without known PCOS. Full-Text PDF

Background Metformin is an oral anti-hyperglycemic agent used in the treatment of type 2 diabetes mellitus. The results of the UK Prospective Diabetes Study indicate that metformin treatment is associated with a reduction in total mortality compared to other anti-hyperglycemic treatments. Metformin, however, is thought to increase the risk of lactic acidosis, and is considered to be contraindicated in many chronic hypoxemic conditions that may be associated with lactic acidosis, such as cardiovascular, renal, hepatic and pulmonary disease, and advancing age.Objectives To assess the incidence of fatal and nonfatal lactic acidosis with metformin use compared to placebo and other glucose-lowering treatments in patients with type 2 diabetes mellitus. A secondary objective was to evaluate the blood lactate levels for those on metformin treatment compared to placebo or non-metformin therapies.Search strategy A search was performed of The Cochrane Library (up to 8/2005), MEDLINE (up to 8/2005), EMBASE (up to 11/2000), OLD MEDLINE, and REACTIONS (up to 8/2005), in order to identify all studies of metformin treatment from 1966 to August 2005. The Cumulated Index Medicus was used to search relevant articles from 1959 to 1965. The search was augmented by scanning references of identified articles, and by contacting principal investigators. Date of latest search: August 2005.Selection criteria Prospective trials in patients with type 2 diabetes that lasted longer than one month were included if they evaluated metformin, alone or in combination with other treatments, compared to placebo or any other glucose-lowering therapy. Observational cohort studies of metformin treatment lasting greater than one month were also included.Data collection and analysis Two reviewers independently selected trials to be included, assessed study quality and extracted data. The incidence of fatal and nonfatal lactic acidosis was recorded as cases per patient-years, for metformin treatment and for placebo or other treatments. The upper limit for the true incidence of cases in the metformin and non-metformin groups were calculated using Poisson statistics. In a second analysis lactate levels were measured as a net change from baseline or as mean treatment values ( basal and stimulated by food or exercise) for treatment and comparison groups. The pooled results were recorded as a weighted mean difference (WMD) in mmol/L, using the fixed effect model for continuous data.Main results Pooled data from 206 comparative trials and cohort studies revealed no cases of fatal or nonfatal lactic acidosis in 47,846 patient-years of metformin use or in 38,221 patients-years in the non-metformin group. Using Poisson statistics with 95% confidence intervals the upper limit for the true incidence of metformin-associated lactic acidosis was 6.3 cases per 100,000 patient-years, and the upper limit for the true incidence of lactic acidosis in the non-metformin group was 7.8 cases per 100,000 patient-years. There was no difference in lactate levels, either as mean treatment levels or as a net change from baseline, for metformin compared to placebo or other non-biguanide therapies. The mean lactate levels were slightly lower for metformin treatment compared to phenformin (WMD -0.75 mmol/L, 95% CI -0.86 to -0.15).Authors' conclusions There is no evidence from prospective comparative trials or from observational cohort studies that metformin is associated with an increased risk of lactic acidosis, or with increased levels of lactate, compared to other anti-hyperglycemic treatments if prescribed under the study conditions.

Background: Long-acting beta-agonists may increase the risk for fatal and nonfatal asthma exacerbations.Purpose: To assess the risk for severe, life-threatening, or fatal asthma exacerbations associated with long-acting beta-agonists.Data Sources: English- and non-English-language searches of MEDLINE, EMBASE, and Cochrane databases; the U.S. Food and Drug Administration Web site; and references of selected reviews through December 2005.Study Selection: Randomized, placebo-controlled trials that lasted at least 3 months and evaluated long-acting P-agonist use in patients with asthma. All trials allowed the use of as-needed short-acting beta-agonists.Data Extraction: outcomes measured were Peto odds ratio (OR) and risk difference of severe exacerbations requiring hospitalization, life-threatening exacerbations requiring intubation and ventilation, and asthma-related deaths. The OR for asthma-related deaths was obtained from the Salmeterol Multi-center Asthma Research Trial (SMART).Data Synthesis: Pooled results from 19 trials with 33 826 participants found that long-acting beta-agonists increased exacerbations requiring hospitalization (OR, 2.6 [95% Cl, 1.6 to 4.3]) and life-threatening exacerbations (OR, 1.8 [Cl, 1.1 to 2.9]) compared with placebo. Hospitalizations were statistically significantly increased with salmeterol (OR, 1.7 [Cl, 1.1 to 2.7]) and formoterol (OR, 3.2 [Cl, 1.7 to 6.0]) and in children (OR, 3.9 [Cl, 1.7 to 8.8]) and adults (OR, 2.0 [Cl, 1.1 to 3.9]). The absolute increase in hospitalization was 0.7% (Cl, 0.1% to 1.3%) over 6 months. The risk for asthma-related deaths was increased (OR, 3.5 [Cl, 1.3 to 9.3]), with a pooled risk difference of 0.07% (Cl, 0.01% to 0.1%).Limitations: The small number of deaths limited the reliability in assessing this risk, and 28 studies did not report information on the outcomes of interest.Conclusions: Long-acting beta-agonists have been shown to increase severe and life-threatening asthma exacerbations, as well as asthma-related deaths.

Thomas Gold, professor emeritus of astronomy at Cornell University, died on 22 June 2004, in Ithaca, New York, of complications from a heart attack. One of the great cosmic thinkers in the past six decades, he questioned with confidence and without hesitation many fundamental physics assumptions. He was an “ideas” man of enormous breadth who many times succeeded in finding the right solutions to prominent problems, such as the nature of pulsars and the mechanism of hearing. Tommy was born in Vienna, Austria, on 22 May 1920. When he was 13, he moved with his family to Berlin, Germany. His family subsequently fled Hitler’s Germany for London because Tommy’s father was of Jewish heritage. Tommy attended a boarding school in Zuoz, Switzerland, and, in 1938, went to Cambridge University as a mechanical engineering student. But when Britain declared war on Germany in 1939, his Austrian citizenship landed him in an enemy alien camp in Canada. He was soon returned to England and was appointed to the British Admiralty Signals Establishment, where, for the rest of the war, he designed radar detection systems, partly in collaboration with Hermann Bondi and Fred Hoyle. He received his BA in mechanical engineering in 1942.Shortly after the war, while a graduate student at Cambridge, Tommy created a model of a positive feedback mechanism in the inner ear to explain the theory of hearing. Other scientists disregarded that work for many decades, but modern theories of hearing incorporate much of it. Gold, Bondi, and Hoyle developed the controversial cosmological theory called the steady state theory, in which the universe maintains a constant appearance, despite its expansion, by creating new matter. The theory had no adjustable constants and was beautiful, even though observations have since disproved it.Tommy accepted a professorship at Harvard University in 1957. He then moved to Cornell in 1959 to build a modern department of astronomy from an almost nonexisting one. He fostered interdisciplinary research as the founder and first director of Cornell’s Center for Radiophysics and Space Research. During his 20 years in that post, the Arecibo Observatory was built in Puerto Rico and is operated by Cornell. Although the observatory was initially designed by Bill Gordon, a Cornell engineering professor, for ionospheric backscatter, Tommy guided its use for radio astronomy. His fertile mind led him into many fascinating areas of research, such as the alignment of galactic dust, the instability of Earth’s axis of rotation, the dusty lunar surface, the Sun’s cosmic rays, and plasmas and magnetic fields in the solar system. Other areas that caught his interest were the origin of solar flares, the nature of time, molecules and masers in the interstellar medium, rotating neutron stars and the nature of pulsars, terrestrial sources of hydrocarbons, and the deep Earth biosphere. Starting in 1961, he discussed the formation and abundance of interstellar molecular hydrogen and pointed out its dynamical importance very close to the Galactic Plane. He was a central figure with NASA during the Apollo Moon missions but disagreed with the agency on several topics and voiced his opposition to the excessive use of humans in space. As early as 1955, he had pointed out that the lunar surface could not be pristine rock. He estimated the thickness of Moon dust; it was a slight overestimate but a good antidote to those who had ignored a loose surface entirely.In 1969, Cambridge awarded Tommy a DSc in recognition of his record of research and publication. He was appointed the John L. Wetherill Professor of Astronomy at Cornell in 1971 and spent the rest of his career at the university until his retirement in 1986.Perhaps Tommy’s greatest contribution came when pulsars were discovered and he explained them as rotating neutron stars, an explanation that has proven correct. However, some of his ideas that have not yet been accepted are still stimulating and thought provoking. One example is his work on the Arrow of Time in terrestrial phenomena, which he claimed is controlled by the direction of the expansion of the universe. Another is his conjecture of very slow accretion onto some cold protostars, which might produce cold white dwarf stars without any hydrogen burning. A more recent idea was that fuel in the form of methane and other hydrocarbons originates deep within Earth as remnants of material included in the planet’s formation. He wrote two books on this subject: Power from the Earth (Orion, 1987) and The Deep Hot Biosphere (Copernicus, 1999). The second discusses microbiology in deep cracks in Earth. Many geologists disagree with the ideas presented in these works, but the concept of “life in cracks” seems to be fairly well accepted.Among many honors, Tommy was a fellow of the Royal Society. He received the Gold Medal of the Royal Astronomical Society in 1985.In his leisure time, Tommy was a competitive skier, both on snow and water. He was also a master carpenter. Whatever project he undertook, he did with enthusiasm and confidence. Many of his ideas were of fundamental importance to physics and astronomy, and those that have survived have been outstanding contributions. Thomas Gold DEPT. OF ASTRONOMY, CORNELL U.PPT|High resolution© 2005 American Institute of Physics.

Both in astronomy and in medicine research, fallacies occur occasionally. Sometimes these fallacies are due to 'subconscious cheating' or the 'file drawer effect' (filing away unfavourable results instead of publishing), but it is difficult to know whether a fallacy has occurred and, if so, why. I give two examples from the past where, in my opinion, fallacies have occurred: a quadratic distance-redshift law and a periodicity in galaxy pair redshift differences. I then discuss the current quasi steady state cosmology, which is very unorthodox but it is not yet clear if fallacies have occurred. I finish with examples from medicine research, where fallacies are particularly troublesome and some countermeasures are attempted.