Do clinicians understand the size of treatment effects? A randomized survey across 8 countries.

BACKGROUND Meta-analyses of continuous outcomes typically provide enough information for decision-makers to evaluate the extent to which chance can explain apparent differences between interventions. The interpretation of the magnitude of these differences - from trivial to large - can, however, be challenging. We investigated clinicians' understanding and perceptions of usefulness of 6 statistical formats for presenting continuous outcomes from meta-analyses (standardized mean difference, minimal important difference units, mean difference in natural units, ratio of means, relative risk and risk difference). METHODS We invited 610 staff and trainees in internal medicine and family medicine programs in 8 countries to participate. Paper-based, self-administered questionnaires presented summary estimates of hypothetical interventions versus placebo for chronic pain. The estimates showed either a small or a large effect for each of the 6 statistical formats for presenting continuous outcomes. Questions addressed participants' understanding of the magnitude of treatment effects and their perception of the usefulness of the presentation format. We randomly assigned participants 1 of 4 versions of the questionnaire, each with a different effect size (large or small) and presentation order for the 6 formats (1 to 6, or 6 to 1). RESULTS Overall, 531 (87.0%) of the clinicians responded. Respondents best understood risk difference, followed by relative risk and ratio of means. Similarly, they perceived the dichotomous presentation of continuous outcomes (relative risk and risk difference) to be most useful. Presenting results as a standardized mean difference, the longest standing and most widely used approach, was poorly understood and perceived as least useful. INTERPRETATION None of the presentation formats were well understood or perceived as extremely useful. Clinicians best understood the dichotomous presentations of continuous outcomes and perceived them to be the most useful. Further initiatives to help clinicians better grasp the magnitude of the treatment effect are needed.

Description of the SAGhE Cohort: A Large European Study of Mortality and Cancer Incidence Risks after Childhood Treatment with Recombinant Growth Hormone.

BACKGROUND The long-term safety of growth hormone treatment is uncertain. Raised risks of death and certain cancers have been reported inconsistently, based on limited data or short-term follow-up by pharmaceutical companies. PATIENTS AND METHODS The SAGhE (Safety and Appropriateness of Growth Hormone Treatments in Europe) study assembled cohorts of patients treated in childhood with recombinant human growth hormone (r-hGH) in 8 European countries since the first use of this treatment in 1984 and followed them for cause-specific mortality and cancer incidence. Expected rates were obtained from national and local general population data. The cohort consisted of 24,232 patients, most commonly treated for isolated growth failure (53%), Turner syndrome (13%) and growth hormone deficiency linked to neoplasia (12%). This paper describes in detail the study design, methods and data collection and discusses the strengths, biases and weaknesses consequent on this. CONCLUSION The SAGhE cohort is the largest and longest follow-up cohort study of growth hormone-treated patients with follow-up and analysis independent of industry. It forms a major resource for investigating cancer and mortality risks in r-hGH patients. The interpretation of SAGhE results, however, will need to take account of the methods of cohort assembly and follow-up in each country.

Results of the Questionnaire

Early diagnosis of patients with compensated advanced chronic liver disease (cACLD) and portal hypertension is challenging in clinical practice. A growing amount of evidence regarding noninvasive diagnostic methods, and in particular liver stiffness measurement (LSM), suggests that these tools could be used in clinical practice and might potentially limit the use of invasive, reference diagnostic tools (HVPG measurement and endoscopy). Our panel aimed at better understanding the opinion of the Baveno faculty regarding the current practice and use of invasive and noninvasive methods in the field of screening and surveillance of varices; a specific questionnaire was electronically sent to all the faculty members. The results suggested that the experts agreed on the use of noninvasive methods to rule out/identify patients with cACLD. They also indicated that the persistence or removal of the causal agent which led to cirrhosis should guide the choice of using the shortest or the longest interval among those recommended for surveillance endoscopies. Finally, the use of noninvasive methods in these clinical scenarios was pointed out as a relevant field for future research.

GLUCAGON GENE EXPRESSION: ANALYSIS OF PREPROGLUCAGON

Glucagon is a 29 amino acid polypeptide hormone produced in the (alpha) cells of the pancreatic islets. The purpose of this research was to understand better the role of glucagon in the regulation of metabolic processes. As with other polypeptide hormones, the synthesis of glucagon is thought to involve a larger precursor, which is then enzymatically cleaved to the functional form. The specific research objectives were to obtain cloned copies of the messenger RNA (mRNA) for pancreatic glucagon, to determine their primary sequences, and from this coding information to deduce the amino acid sequence of the initial glucagon precursor. From this suggested preproglucagon sequence and prior information on possible proglucagon intermediate processing products, the overall objective of this research is to propose a possible pathway for the biosynthesis of pancreatic glucagon.^ Synthetic oligodeoxynucleotide probes of 14-nucleotides (14-mer) and 17-nucleotides (a 17-mer) complementary to codons specifying a unique sequence of mature glucagon were synthesized. The ('32)P-labeled-14-mer was hybridized with size-fractionated fetal bovine pancreatic poly(A('+))RNA bound to nitrocellulose. RNA fractions of (TURN)14S were found to hybridize specifically, resulting in an (TURN)10-fold enrichment for these sequences. These poly(A('+))RNAs were translated in a cell-free system and the products analyzed by gel electrophoresis. The translation products were found to be enriched for a protein of the putative size of mammalian preproglucagon ((TURN)21 kd). These enriched RNA fractions were used to construct a complementary DNA (cDNA) library is plasmid pBR322.^ Screening of duplicate colony filters with the ('32)P-labeled-17-mer and a ('32)P-labeled-17-mer-primed cDNA probe indicated 25 possible glucagon clones from 3100 colonies screened. Restriction mapping of 6 of these clones suggested that they represented a single mRNA species. Primary sequence analysis of one clone containing a 1200 base pair DNA insert revealed that it contained essentially a full-length copy of glucagon cDNA.^ Analaysis of the cDNA suggested that it encoded an initial translation product of 180 amino acids with an M(,r) = 21 kd. The first initiation codon (ATG, methionine) followed by the longest open reading frame of 540 nucleotides was preceded by a 5'-untranslated region of 90 nucleotides, and was followed by a longer 3'-untranslated region of 471 nucleotides, resulting in a total of 1101 nucleotides. . . . (Author's abstract exceeds stipulated maximum length. Discontinued here with permission of author.) UMI ^

Zuni elders: Ethnography of American Indian aging

Problem/purpose. The specific aim of this focused ethnography was to provide insight into the experience of aging of the American Indian (AI) elder as demonstrated by one tribe, the Zuni of New Mexico. Discovering how Zuni elders construct the experience of aging and the associated behaviors allowed the researcher to deconstruct aging and then re-present it in a cogent description for this population. Such a description is lacking in the literature and will be useful in planning for culturally relevant eldercare services. ^ Methods. Ethnographic field techniques were used to sample from elders, pueblo members-at-large, activities, events and places. Over 1800 hrs were spent in the field spanning 14 months and five site visits, with the longest at almost 4 weeks. Developing codes for transcribed interviews, field notes, supplementary documents, photographs, videos, and artifacts was carried out during analysis. Categories and ultimately a cognitive map and model were developed which represented aging in Zuni Pueblo in 2000. ^ Findings. Zuni elders are aging in two worlds. Their primary world has been described as a sevenfold universe, a complicated structure with seven planes wherein the middle plane refers to themselves, a synthesis of all the other planes. The increasing influence of the white world has formed a ‘new middle’ out of which everyday aspects of aging are viewed. ^ Implications for nursing/gerontology. Nurses and others in gerontology must recognize that vast differences in worldviews are present between themselves and AI elders regarding health practices, spirituality, eating patterns, family roles, medicine, religion and countless other aspects of life. Their centuries old beliefs and practices drive these differences coupled with a collision with the white world. Making a paradigm shift using an appropriate lens with which to view these differences can only increase our understanding and efficacy in delivering culturally relevant care. ^

Predator-Induced Plasticity in Spotted Salamanders (Ambystoma maculatum)

The ability to respond plastically to the environment has allowed amphibians to evolve adaptive responses to spatial and temporal variation in predation threat. However, animals exposed to predators may also show costs of plasticity or tradeoffs. This study examines predator-induced plasticity in larval development, behavior, and metamorphosis in the spotted salamander, Ambystoma maculatum. Salamanders were raised in two treatments: with predator cues (a fish predator, genus Lepomis, on the other side of a divided tank), or without predator cues. During the larval stage the predator treatment group experienced higher mortality rates than the no-predator treatment group. Behavioral trials revealed that predator treatment animals ate less than those not exposed, and that this feeding response was immediately inducible and had lasting effects. Animals in the predator treatment group had smaller tail areas during the mid-larval period. Feeding and body size effects may have contributed to increased mortality in the predator-treatment animals. The timing of metamorphic onset was not affected by the presence of predators, but predator-treatment salamanders had shorter snout/vent lengths at metamorphosis. The duration of metamorphosis showed a potentially adaptive plastic response to the presence of predator cues: metamorphosis was longest in the no-predator treatment group, reduced in the predator treatment group, and even further reduced for animals exposed to predator cues only during metamorphosis. Overall, we found a mix of potentially adaptive and costly plastic responses in spotted salamanders.

Isotone Recursive Methods for Overlapping Generation Models with Stochastic Nonclassical Production

Based on an order-theoretic approach, we derive sufficient conditions for the existence, characterization, and computation of Markovian equilibrium decision processes and stationary Markov equilibrium on minimal state spaces for a large class of stochastic overlapping generations models. In contrast to all previous work, we consider reduced-form stochastic production technologies that allow for a broad set of equilibrium distortions such as public policy distortions, social security, monetary equilibrium, and production nonconvexities. Our order-based methods are constructive, and we provide monotone iterative algorithms for computing extremal stationary Markov equilibrium decision processes and equilibrium invariant distributions, while avoiding many of the problems associated with the existence of indeterminacies that have been well-documented in previous work. We provide important results for existence of Markov equilibria for the case where capital income is not increasing in the aggregate stock. Finally, we conclude with examples common in macroeconomics such as models with fiat money and social security. We also show how some of our results extend to settings with unbounded state spaces.

Stationary Markovian Equilibrium in Overlapping Generation Models with Stochastic Nonclassical Production

This paper provides new sufficient conditions for the existence, computation via successive approximations, and stability of Markovian equilibrium decision processes for a large class of OLG models with stochastic nonclassical production. Our notion of stability is existence of stationary Markovian equilibrium. With a nonclassical production, our economies encompass a large class of OLG models with public policy, valued fiat money, production externalities, and Markov shocks to production. Our approach combines aspects of both topological and order theoretic fixed point theory, and provides the basis of globally stable numerical iteration procedures for computing extremal Markovian equilibrium objects. In addition to new theoretical results on existence and computation, we provide some monotone comparative statics results on the space of economies.

Risk of adult-onset asthma in Mexican-American women employed in food preparation or food service

Existing literature examining the association between occupation and asthma has not been adequately powered to address this question in the food preparation or food service industries. Few studies have addressed the possible link between occupational exposure to cooking fumes and asthma. This secondary analysis of cohort study data aimed to investigate the association between adult-onset asthma and exposure to: (a) cooking fumes at work or (b) longest-held employment in food preparation or food service (e.g. waiters and waitresses, food preparation workers, non-restaurant food servers, etc.). Participants arose from a cohort of Mexican-American women residing in Houston, TX, recruited between July 2001 and June 2007. This analysis used Cox proportional-hazards regression to estimate the hazard ratio of adult-onset asthma given the exposures of interest, adjusting for age, BMI, smoking status, acculturation, and birthplace. We found a strong association between adult-onset asthma and occupational exposure to cooking fumes (hazard ratio [HR] = 1.77; 95% confidence interval [CI], 1.15, 2.72), especially in participants whose longest-held occupation was not in the food-related industry (HR = 2.12; 95% CI, 1.21, 3.60). In conclusion, adult-onset asthma is a serious public health concern for food industry workers. ^

Mathematical and empirical examinations of some epidemiological procedures

In epidemiology literature, it is often required to investigate the relationships between means where the levels of experiment are actually monotone sets forming a partition on the range of sampling values. With this need, the analysis of these group means is generally performed using classical analysis of variance (ANOVA). However, this method has never been challenged. In this dissertation, we will formulate and present our examination of its validity. First, the classical assumptions of normality and constant variance are not always true. Second, under the null hypothesis of equal means, the test statistic for the classical ANOVA technique is still valid. Third, when the hypothesis of equal means is rejected, the classical analysis techniques for hypotheses of contrasts are not valid. Fourth, under the alternative hypothesis, we can show that the monotone property of levels leads to the conclusion that the means are monotone. Fifth, we propose an appropriate method for handing the data in this situation. ^

Health significance of chlorination byproducts in drinking water: The Houston experience: A continuation study

Background. Houston, Texas, once obtained all its drinking water from underground sources. However, in 1853, the city began supplementing its water from the surface source Lake Houston. This created differences in the exposure to disinfection byproducts (DBPs) in different parts of Houston. Trihalomethanes (THMs) are the most common DBP and are useful indicators of DBPs in treated drinking water. This study examines the relationship between THMs in chlorinated drinking water and the incidence of bladder cancer in Houston. ^ Methods. Individual bladder cancer deaths, from 1975 to 2004, were assigned to four surface water exposure areas in Houston utilizing census tracts—area A used groundwater the longest, area B used treated lake water the longest, area C used treated lake water the second longest, and area D used a combination of groundwater and treated lake water. Within each surface water exposure area mortality rates were calculated in 5 year intervals by four race-gender categories. Linear regression models were fitted to the bladder cancer mortality rates over the entire period of available data (1990–2004). ^ Results. A decrease in bladder cancer mortality was observed amongst white males in area B (p = 0.030), white females in area A (p = 0.008), non-white males in area D (p = 0.003), and non-white females in areas A and B (p = 0.002 & 0.001). Bladder cancer mortality differed by race-gender and time (p ≤ 0.001 & p ≤ 0.001), but not by surface water exposure area (p = 0.876). ^ Conclusion. The relationship between bladder cancer mortality and the four surface water exposure areas (signifying THM exposure) was insignificant. This result could be attributable to Houston controlling for THMs starting in the early 1980’s by using chloramine as a secondary disinfectant in the drinking water purification process.^

Occupation and glioma: The Harris County Brain Tumor Study, 2001--2010

The relationship between occupational exposures and glioma has not been adequately assessed due to the lack of studies in current scientific literature. To address this disparity, the Harris County Brain Tumor Study, an ongoing population-based case-control study, began in January 2001. Longest-held occupation for 382 cases and 629 controls were frequency matched on age (within 5 years), sex, and race and placed into 14 predetermined occupational categories. Adjusted odds ratios and 95% confidence intervals were calculated for each category using multiple logistic regression. Potential confounders assessed included sex, age, smoking status, education and income. For all subjects, significantly elevated adjusted odds ratios were found in health-related (aOR=1.66; 95%CI=1.03, 2.68), teaching (aOR=1.84; 95%CI=1.17, 2.88), and protective service (aOR=3.6; 95%CI=1.05, 12.31) occupational categories after controlling for sex and education. A significantly lowered odds ratio was seen in the writers, artists, and entertainers category (aOR=0.14; 95%CI=0.03, 0.58). In the stratified analyses, which controlled for education, males had a significantly elevated odds ratio for protective service workers (aOR=4.83; 95%CI=1.24, 18.83) while a significantly lower odds ratio was found in mechanics and machine operators (aOR=0.33; 95%CI=0.12,0.87). In females, we observed a significantly elevated odds ratio in teachers (aOR=1.99; 95%CI=1.20,3.31) and a significantly lower odds ratio in clerical workers (aOR=0.63; 95%CI=0.45,0.90). These analyses revealed several significant associations and allowed for separate analyses by gender, distinguishing this study from many glioma studies. Further analyses should provide a large enough sample size to stratify by gender as well as histological subtype.^

Motivational interviewing and feedback for college drinkers: Handling missing values with complete case analysis and multiple imputation

Objective: In this secondary data analysis, three statistical methodologies were implemented to handle cases with missing data in a motivational interviewing and feedback study. The aim was to evaluate the impact that these methodologies have on the data analysis. ^ Methods: We first evaluated whether the assumption of missing completely at random held for this study. We then proceeded to conduct a secondary data analysis using a mixed linear model to handle missing data with three methodologies (a) complete case analysis, (b) multiple imputation with explicit model containing outcome variables, time, and the interaction of time and treatment, and (c) multiple imputation with explicit model containing outcome variables, time, the interaction of time and treatment, and additional covariates (e.g., age, gender, smoke, years in school, marital status, housing, race/ethnicity, and if participants play on athletic team). Several comparisons were conducted including the following ones: 1) the motivation interviewing with feedback group (MIF) vs. the assessment only group (AO), the motivation interviewing group (MIO) vs. AO, and the intervention of the feedback only group (FBO) vs. AO, 2) MIF vs. FBO, and 3) MIF vs. MIO.^ Results: We first evaluated the patterns of missingness in this study, which indicated that about 13% of participants showed monotone missing patterns, and about 3.5% showed non-monotone missing patterns. Then we evaluated the assumption of missing completely at random by Little's missing completely at random (MCAR) test, in which the Chi-Square test statistic was 167.8 with 125 degrees of freedom, and its associated p-value was p=0.006, which indicated that the data could not be assumed to be missing completely at random. After that, we compared if the three different strategies reached the same results. For the comparison between MIF and AO as well as the comparison between MIF and FBO, only the multiple imputation with additional covariates by uncongenial and congenial models reached different results. For the comparison between MIF and MIO, all the methodologies for handling missing values obtained different results. ^ Discussions: The study indicated that, first, missingness was crucial in this study. Second, to understand the assumptions of the model was important since we could not identify if the data were missing at random or missing not at random. Therefore, future researches should focus on exploring more sensitivity analyses under missing not at random assumption.^

Zircons, isotope ratios and element analyses from tonalite and oxide gabbro of the mid-ocean ridge from ODP Hole 176-735B

A limiting factor in the accuracy and precision of U/Pb zircon dates is accurate correction for initial disequilibrium in the 238U and 235U decay chains. The longest-lived-and therefore most abundant-intermediate daughter product in the 235U isotopic decay chain is 231Pa (T1/2 = 32.71 ka), and the partitioning behavior of Pa in zircon is not well constrained. Here we report high-precision thermal ionization mass spectrometry (TIMS) U-Pb zircon data from two samples from Ocean Drilling Program (ODP) Hole 735B, which show evidence for incorporation of excess 231Pa during zircon crystallization. The most precise analyses from the two samples have consistent Th-corrected 206Pb/238U dates with weighted means of 11.9325 ± 0.0039 Ma (n = 9) and 11.920 ± 0.011 Ma (n = 4), but distinctly older 207Pb/235U dates that vary from 12.330 ± 0.048 Ma to 12.140 ± 0.044 Ma and 12.03 ± 0.24 to 12.40 ± 0.27 Ma, respectively. If the excess 207Pb is due to variable initial excess 231Pa, calculated initial (231Pa)/(235U) activity ratios for the two samples range from 5.6 ± 1.0 to 9.6 ± 1.1 and 3.5 ± 5.2 to 11.4 ± 5.8. The data from the more precisely dated sample yields estimated DPazircon/DUzircon from 2.2-3.8 and 5.6-9.6, assuming (231Pa)/(235U) of the melt equal to the global average of recently erupted mid-ocean ridge basaltic glasses or secular equilibrium, respectively. High precision ID-TIMS analyses from nine additional samples from Hole 735B and nearby Hole 1105A suggest similar partitioning. The lower range of DPazircon/DUzircon is consistent with ion microprobe measurements of 231Pa in zircons from Holocene and Pleistocene rhyolitic eruptions (Schmitt (2007; doi:10.2138/am.2007.2449) and Schmitt (2011; doi:10.1146/annurev-earth-040610-133330)). The data suggest that 231Pa is preferentially incorporated during zircon crystallization over a range of magmatic compositions, and excess initial 231Pa may be more common in zircons than acknowledged. The degree of initial disequilibrium in the 235U decay chain suggested by the data from this study, and other recent high precision datasets, leads to resolvable discordance in high precision dates of Cenozoic to Mesozoic zircons. Minor discordance in zircons of this age may therefore reflect initial excess 231Pa and does not require either inheritance or Pb loss.

Stable isotope ratios and chemistry on corals from the Caribbean Sea

Instrumental climate data are limited in length and only available with low spatial coverage before the middle of the 20th century. This is too short to reliably determine and interpret decadal and longer scale climate variability and to understand the underlying mechanisms with sufficient accuracy. A proper knowledge of past variability of the climate system is needed to assess the anthropogenic impact on climate and ecosystems, and also important with regard to long-range climate forecasting. Highly-resolved records of past climate variations that extend beyond pre-industrial times can significantly help to understand long-term climate changes and trends. Indirect information on past environmental and climatic conditions can be deduced from climate-sensitive proxies. Large colonies of massive growing tropical reef corals have been proven to sensitively monitor changes in ambient seawater. Rapid skeletal growth, typically ranging between several millimeters to centimeters per year, allows the development of proxy records at sub-seasonal resolution. Stable oxygen isotopic composition and trace elemental ratios incorporated in the aragonitic coral skeleton can reveal a detailed history of past environmental conditions, e.g., sea surface temperature (SST). In general, coral-based reconstructions from the tropical Atlantic region have lagged behind the extensive work published using coral records from the Indian and Pacific Oceans. Difficulties in the analysis of previously utilized coral archives from the Atlantic, typically corals of the genera Montastrea and Siderastrea, have so far exacerbated the production of long-term high-resolution proxy records. The objective of this study is the evaluation of massive fast-growing corals of the species Diploria strigosa as a new marine archive for climate reconstructions from the tropical Atlantic region. For this purpose, coral records from two study sites in the eastern Caribbean Sea (Guadeloupe, Lesser Antilles; and Archipelago Los Roques, Venezuela) were examined. At Guadeloupe, a century-long monthly resolved multi-proxy coral record was generated. Results present the first d18O (Sr/Ca)-SST calibration equations for the Atlantic braincoral Diploria strigosa, that are robust and consistent with previously published values using other coral species from different regions. Both proxies reflect local variability of SST on a sub-seasonal scale, which is a precondition for studying seasonally phase-locked climate variations, as well as track variability on a larger spatial scale (i.e., in the Caribbean and tropical North Atlantic). Coral Sr/Ca reliably records local annual to interannual temperature variations and is higher correlated to in-situ air temperature than to grid-SST. The warming calculated from coral Sr/Ca is concurrent with the strong surface temperature increase at the study site during the past decades. Proxy data show a close relationship to major climate signals from the tropical Pacific and North Atlantic (the El Niño Southern Oscillation (ENSO) and the North Atlantic Oscillation (NAO)) affecting the seasonal cycle of SST in the North Tropical Atlantic (NTA). Coral oxygen isotopes are also influenced by seawater d18O (d18Osw) which is linked to the hydrological cycle, and capture large-scale climate variability in the NTA region better than Sr/Ca. Results from a quantitative comparison between extreme events in the two most prominent modes of external forcing, namely the ENSO and NAO, and respective events recorded in seasonal coral d18O imply that SST variability at the study site is highly linked to Pacific and North Atlantic variability, by this means supporting the assumptions of observational- and model-based studies which suggest a strong impact of ENSO and NAO forcings onto the NTA region through a modulation of trade wind strength in winter. Results from different spectral analysis tools suggest that interannual climate variability recorded by the coral proxies is II largely dictated by Pacific ENSO forcing, whereas at decadal and longer timescales the influence of the NAO is dominan. tThe Archipelago Los Roques is situated in the southeastern Caribbean Sea, north of the Venezuelan coast. Year-to-year variations in monthly resolved coral d18O of a nearcentury- long Diploria strigosa record are significantly correlated with SST and show pronounced multidecadal variations. About half of the variance in coral d18O can be explained by variations in seawater d18O, which can be estimated by calculating the d18Oresidual via subtracting the SST component from measured coral d18O. The d18Oresidual and a regional precipitation index are highly correlated at low frequencies, suggesting that d18Osw variations are primarily atmospheric-driven. Warmer SSTs at Los Roques broadly coincide with higher precipitation in the southeastern Caribbean at multidecadal time scales, effectively strengthening the climate signal in the coral d18O record. The Los Roques coral d18O record displays a strong and statistically significant relationship to different indices of hurricane activity during the peak of the Atlantic hurricane season in boreal summer and is a particularly good indicator of decadal-multidecadal swings in the latter indices. In general, the detection of long-term changes and trends in Atlantic hurricane activity is hampered due to the limited length of the reliable instrumental record and the known inhomogeneity in the observational databases which result from changes in observing practice and technology over the years. The results suggest that coral-derived proxy data from Los Roques can be used to infer changes in past hurricane activity on timescales that extend well beyond the reliable record. In addition, the coral record exhibits a clear negative trend superimposed on the decadal to multidecadal cycles, indicating a significant warming and freshening of surface waters in the genesis region of tropical cyclones during the past decades. The presented coral d18O time series provides the first and, so far, longest continuous coral-based record of hurricane activity. It appears that the combination of both signals (SST and d18Osw) in coral d18O leads to an amplification of large-scale climate signals in the record, and makes coral d18O even a better proxy for hurricane activity than SST alone. Atlantic hurricane activity naturally exhibits strong multidecadal variations that are associated with the Atlantic Multidecadal Oscillation (AMO), the major mode of lowfrequency variability in the North Atlantic Ocean. However, the mechanisms underlying this multidecadal variability remain controversial, primarily because of the limited instrumental record. The Los Roques coral d18O displays strong multidecadal variability with a period of approximately 60 years that is closely related to the AMO, making the Archipelago Los Roques a very sensitive location for studying low-frequency climate variability in the Atlantic Ocean. In summary, the coral records presented in this thesis capture different key climate variables in the north tropical Atlantic region very well, indicating that fast-growing Diploria strigosa corals represent a promising marine archive for further proxy-based reconstructions of past climate variability on a range of time scales.