J-shaped relation between change in diastolic blood pressure and progression of aortic atherosclerosis

The J-shaped relation between diastolic blood pressure and mortality from coronary heart disease continues to provoke controversy. We examined the association between diastolic blood pressure and progression of aortic atherosclerosis in a population-based cohort of 855 women, aged 45-64 years at baseline. The women were examined radiographically for calcified deposits in the abdominal aorta, which have been shown to reflect intimal atherosclerosis. After 9 years of follow-up, slight progression of atherosclerosis was noted in 19% of women and substantial progression in 16%. The age-adjusted relative risk of substantial atherosclerotic progression in women with a decrease in diastolic pressure of 10 mm Hg or more was 2·5 (95% CI 1·3-5·6), compared with the reference group of women who had a smaller decrease or no change. The excess risk in this group was confined to women whose increase in pulse pressure was above the median (3·9 [1·5-9·9] vs 1·1 [0 3-4·2] in women with an increase in pulse pressure below the median). The relative risks for women with rises in diastolic pressure of 1-9 mm Hg and 10 mm Hg or more were 2·2 (1 1-4 3) and 3·5 (1 6-8 0), respectively. These findings suggest that a decline in diastolic blood pressure indicates vessel wall stiffening associated with atherosclerotic progression. They support the hypothesis that in low-risk subjects progression of atherosclerosis may be accompanied by a decrease in diastolic blood pressure rather than the opposing idea that low diastolic blood pressure precipitates the occurrence of atherosclerotic events

Investigation of the association of the CRTM and CRTL1 genes with radiographically evident osteoarthritis in subjects from the Rotterdam study

__Objective:__ To investigate whether radiographically evident osteoarthritis (ROA) in 55-65-year-old men and women is associated with specific alleles or genotypes of the cartilage matrix protein (CRTM) and cartilage link protein (CRTLl) genes. __Methods:__ Cases were selected from a populationbased study on the presence of ROA of the knee or hip. Further radiographic analysis included scoring for spine and hand ROA. Controls, selected from the same population, were free of ROA in all joints. __Results:__ The CRTM locus was significantly associated with hip ROA in men (odds ratio 0.50, 95% confidence interval 0.26-0.95). A significant association between ROA and the CRTLl gene was not observed. __Conclusion:__ These results suggest that the CRTM locus may play a role in the sex- and joint site-specific pattern of ROA development

Trastuzumab plus pertuzumab for HER2-amplified advanced colorectal cancer: Results from the drug rediscovery protocol (DRUP)

BACKGROUND: In 2-5% of patients with colorectal cancer (CRC), human epidermal growth factor 2 (HER2) is amplified or overexpressed. Despite prior evidence that anti-HER2 therapy confers clinical benefit (CB) in one-third of these patients, it is not approved for this indication in Europe. In the Drug Rediscovery Protocol (DRUP), patients are treated with off-label drugs based on their molecular profile. Here, we present the results of the cohort 'trastuzumab/pertuzumab for treatment-refractory patients with RAS/BRAF-wild-type HER2amplified metastatic CRC (HER2+mCRC)'. METHODS: Patients with progressive treatment-refractory RAS/BRAF-wild-type HER2+mCRC with measurable disease were included for trastuzumab plus pertuzumab treatment. Primary endpoints of DRUP are CB (defined as confirmed objective response (OR) or stable disease (SD) ≥ 16 weeks) and safety. Patients were enrolled using a Simon-like 2-stage model, with 8 patients in stage 1 and 24 patients in stage 2 if at least 1/8 patients had CB. To identify biomarkers for response, whole genome sequencing (WGS) was performed on pre-treatment biopsies. RESULTS: CB was observed in 11/24 evaluable patients (46%) with HER2+mCRC, seven patients achieved an OR (29%). Median duration of response was 8.4 months. Patients had undergone a median of 3 prior treatment lines. Median progression-free survival and overall survival were 4.3 months (95% CI 1.9-10.3) and 8.2 months (95% CI 7.2-14.7), respectively. No unexpected toxicities were observed. WGS provided potential explanations for resistance in 3/10 patients without CB, for whom WGS was available. CONCLUSIONS: The results of this study confirm a clinically significant benefit of trastuzumab plus pertuzumab treatment in patients with HER2+mCRC

A phylogenetic classification of the world’s tropical forests

Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition and dynamics. Such understanding will enable anticipation of region specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present the first classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (1) Indo-Pacific, (2) Subtropical, (3) African, (4) American, and (5) Dry forests. Our results do not support the traditional Neo- versus Palaeo-tropical forest division, but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar and India. Additionally, a northern hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern hemisphere forests

An estimate of the number of tropical tree species

The high species richness of tropical forests has long been recognized, yet there remains substantial uncertainty regarding the actual number of tropical tree species. Using a pantropical tree inventory database from closed canopy forests, consisting of 657,630 trees belonging to 11,371 species, we use a fitted value of Fisher’s alpha and an approximate pantropical stem total to estimate the minimum number of tropical forest tree species to fall between ∼40,000 and ∼53,000, i.e. at the high end of previous estimates. Contrary to common assumption, the Indo-Pacific region was found to be as species-rich as the Neotropics, with both regions having a minimum of ∼19,000–25,000 tree species. Continental Africa is relatively depauperate with a minimum of ∼4,500–6,000 tree species. Very few species are shared among the African, American, and the Indo-Pacific regions. We provide a methodological framework for estimating species richness in trees that may help refine species richness estimates of tree-dependent taxa

Phylogenetic classification of the world's tropical forests

Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.</p

A five year prospective study of rheumatoid factor tests in juvenile rheumatoid arthritis A preliminary report of this paper was presented at the annual meeting of the American Rheumatism Association, San Francisco, Calif., June 1964.

No Abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/37706/1/1780100202_ftp.pd

Alcohol and mortality. Results from the EPOZ (Epidemiologic Study of Cardiovascular Risk Indicators) follow-up study

To investigate the association of alcohol intake with mortality from all causes, cardiovascular disease (CVD), cancer and other causes (e.g., accidents, violence, suicide), we performed an analysis of data obtained in a prospective follow-up study conducted in the Netherlands since 1977. Causes of death were defined for a cohort of 1,620 persons (760 men and 860 women) examined in 1977. During the 10-year follow-up period, 123 (7.6%) of the participants died. Frequency of alcohol consumption was obtained separately for wine, beer and liquor by means of a questionnaire. Although no significant association could be established between alcohol consumption and all-cause mortality, all-cause mortality tended to be lower in alcohol consumers compared to abstainers. The age- and sex-adjusted risk estimates of death from CVD were 0.29 (0.11-0.74), 0.46 (0.21-0.96) and 0.32 (0.13-0.77) for subjects with occasional, frequent and daily alcohol use, respectively, compared with those who did not drink at baseline. The mortality risks of never-drinkers and ex-drinkers were similar. A J- or U-shaped relation between alcohol consumption and CVD mortality could not be confirmed in our data but the available information on the amount of alcohol consumed was limited. No significant influence on the risk estimates of death from cancer or other causes was found. However, mortality tended to be higher for those who consumed more alcohol. The protective effect of alcohol intake on CVD mortality found in our data persisted after excluding subjects with cardiovascular or other major diseases at baseline from the analysis

Serum copper and zinc and the risk of death from cancer and cardiovascular disease

To investigate the association of serum copper and zinc with mortality from cancer and cardiovascular disease, the authors performed a case-control analysis of data obtained in a Dutch prospective follow-up study. Cancer (n = 64) and cardiovascular disease (n = 62) deaths and their matched controls were taken from a cohort of 10,532 persons examined in 1975-1978. Trace elements were measured in baseline serum samples, which had been stored during the six to nine years of follow-up. The adjusted risk of death from cancer and cardiovascular disease was about four times higher for subjects in the highest serum copper quintile (greater than 1.43 mg/liter) compared with those with normal levels. The excess mortality observed in subjects with low copper status suggests a U-shaped relation. No significant change in the risk of death from cancer and cardiovascular disease was found for subjects with low or high baseline levels of serum zinc. However, a protective effect of a high zinc status on the risk of cancer and cardiovascular disease is compatible with the data. For definitive conclusions, analysis of larger prospective data sets is recommended