Alcohol email assessment and feedback study dismantling effectiveness for university students (AMADEUS-1): study protocol for a randomized controlled trial

BACKGROUND: Alcohol causes huge problems for population health and for society, which require interventions with individuals as well as populations to prevent and reduce harms. Brief interventions can be effective and increasingly take advantage of the internet to reach high-risk groups such as students. The research literature on the effectiveness of online interventions is developing rapidly and is confronted by methodological challenges common to other areas of e-health including attrition and assessment reactivity and in the design of control conditions. METHODS/DESIGN: The study aim is to evaluate the effectiveness of a brief online intervention, employing a randomized controlled trial (RCT) design that takes account of baseline assessment reactivity, and other possible effects of the research process. Outcomes will be evaluated after 3 months both among student populations as a whole including for a randomized no contact control group and among those who are risky drinkers randomized to brief assessment and feedback (routine practice) or to brief assessment only. A three-arm parallel groups trial will also allow exploration of the magnitude of the feedback and assessment component effects. The trial will be undertaken simultaneously in 2 universities randomizing approximately 15,300 students who will all be blinded to trial participation. All participants will be offered routine practice intervention at the end of the study. DISCUSSION: This trial informs the development of routine service delivery in Swedish universities and more broadly contributes a new approach to the study of the effectiveness of online interventions in student populations, with relevance to behaviors other than alcohol consumption. The use of blinding and deception in this study raise ethical issues that warrant further attention. TRIAL REGISTRATION: ISRCTN28328154

Cardiovascular responses to cognitive stress in patients with migraine and tension-type headache

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to investigate the temporal relationship between autonomic changes and pain activation in migraine and tension-type headache induced by stress in a model relevant for everyday office-work.</p> <p>Methods</p> <p>We measured pain, blood pressure (BP), heart rate (HR) and skin blood flow (BF) during and after controlled low-grade cognitive stress in 22 migraineurs during headache-free periods, 18 patients with tension-type headache (TTH) and 44 healthy controls. The stress lasted for one hour and was followed by 30 minutes of relaxation.</p> <p>Results</p> <p>Cardiovascular responses to cognitive stress in migraine did not differ from those in control subjects. In TTH patients HR was maintained during stress, whereas it decreased for migraineurs and controls. A trend towards a delayed systolic BP response during stress was also observed in TTH. Finger BF recovery was delayed after stress and stress-induced pain was associated with less vasoconstriction in TTH during recovery.</p> <p>Conclusion</p> <p>It is hypothesized that TTH patients have different stress adaptive mechanisms than controls and migraineurs, involving delayed cardiovascular adaptation and reduced pain control system inhibition.</p

Alpha-foetoprotein in umbilical cord in relation to severe pre-eclampsia, birth weight and future breast cancer risk

Women born after pre-eclamptic pregnancies have been reported to be at reduced risk of breast cancer as adults, because of reduced intrauterine oestrogen influence on breast tissue; high levels of α-foetoprotein (a glycoprotein with anti-oestrogenic properties), however, could also be important. In severe pre-eclampsia, placental function and foetal growth are reduced, and umbilical cord plasma levels of α-foetoprotein could reflect the underlying processes. Umbilical cord blood was collected in 12 804 consecutive deliveries. Among 307 pregnancies with clinical pre-eclampsia, 66 singleton pregnancies were identified as clinically severe, and 610 singleton pregnancies were selected as controls. Oestradiol and α-foetoprotein were measured from umbilical plasma, and birth weight was standardized as the ratio between the observed and expected birth weight, adjusted for differences in gestation length and offspring sex. Cord plasma levels of α-foetoprotein were significantly higher in severe pre-eclampsia than controls (P<0.01) after adjustment for gestational age and birth weight. For oestradiol, there was no difference in cord plasma levels between the severe pre-eclampsia group and controls, after adjustment for length of gestation and birth weight. These results suggest that an anti-oestrogenic effect associated with pre-eclampsia may be mediated through high levels of α-foetoprotein rather than low levels of oestradiol

Adult height and risk of breast cancer: a possible effect of early nutrition

The relationship of breast cancer to early reproductive development and height suggests that fetal and childhood nutrition may be important in its aetiology. Caloric restriction sufficient to reduce adult height may reduce breast cancer risk. During World War II (WWII) there was a marked reduction in average caloric intake in Norway that resulted in greater nutritional diversity. We hypothesized that a positive association between height and risk of breast cancer would be stronger among women who were born during this period than among women born before or after the war. A total of 25 204 Norwegian women were followed up for approximately 11 years, and 215 incident cases of breast cancer were registered. We found the strongest positive association between height and breast cancer among women born during WWII: women in the tallest tertile (>167 cm) had a relative risk of 2.5 (95% confidence interval = 1.2–5.5) compared with the shortest (≤ 162 cm). Among women born before or after the war we found no clear association with height. The association with height in the WWII cohort may imply a role for early nutrition in breast cancer aetiology. © 2001 Cancer Research Campaignhttp://www.bjcancer.co

Breast cancer incidence in food- vs non-food-producing areas in Norway: possible beneficial effects of World War II

It has been suggested that World War II influenced breast cancer risk among Norwegian women by affecting adolescent growth. Diet changed substantially during the war, and the reduction in energy intake was assumed to be larger in non-food- producing than in food-producing municipalities. In the present study, we have looked at the influence of residential history in areas with and without food production on the incidence of breast cancer in a population-based cohort study consisting of 597 906 women aged between 30 and 64 years. The study included 7311 cases of breast cancer, diagnosed between 1964 and 1992. The risk estimates were calculated using a Poisson regression model. The results suggest that residential history may influence the risk of breast cancer, where the suggested advantageous effect of World War II seems to be larger in non-food-producing than in food-producing areas. Breast cancer incidence was observed to decline for the post-war cohorts, which is discussed in relation to diet

The progestational and androgenic properties of medroxyprogesterone acetate: gene regulatory overlap with dihydrotestosterone in breast cancer cells

INTRODUCTION: Medroxyprogesterone acetate (MPA), the major progestin used for oral contraception and hormone replacement therapy, has been implicated in increased breast cancer risk. Is this risk due to its progestational or androgenic properties? To address this, we assessed the transcriptional effects of MPA as compared with those of progesterone and dihydrotestosterone (DHT) in human breast cancer cells. METHOD: A new progesterone receptor-negative, androgen receptor-positive human breast cancer cell line, designated Y-AR, was engineered and characterized. Transcription assays using a synthetic promoter/reporter construct, as well as endogenous gene expression profiling comparing progesterone, MPA and DHT, were performed in cells either lacking or containing progesterone receptor and/or androgen receptor. RESULTS: In progesterone receptor-positive cells, MPA was found to be an effective progestin through both progesterone receptor isoforms in transient transcription assays. Interestingly, DHT signaled through progesterone receptor type B. Expression profiling of endogenous progesterone receptor-regulated genes comparing progesterone and MPA suggested that although MPA may be a somewhat more potent progestin than progesterone, it is qualitatively similar to progesterone. To address effects of MPA through androgen receptor, expression profiling was performed comparing progesterone, MPA and DHT using Y-AR cells. These studies showed extensive gene regulatory overlap between DHT and MPA through androgen receptor and none with progesterone. Interestingly, there was no difference between pharmacological MPA and physiological MPA, suggesting that high-dose therapeutic MPA may be superfluous. CONCLUSION: Our comparison of the gene regulatory profiles of MPA and progesterone suggests that, for physiologic hormone replacement therapy, the actions of MPA do not mimic those of endogenous progesterone alone. Clinically, the complex pharmacology of MPA not only influences its side-effect profile; but it is also possible that the increased breast cancer risk and/or the therapeutic efficacy of MPA in cancer treatment is in part mediated by androgen receptor

Detection of a MicroRNA Signal in an In Vivo Expression Set of mRNAs

Background. microRNAs (miRNAs) are approximately 21 nucleotide non-coding transcripts capable of regulating gene expression. The most widely studied mechanism of regulation involves binding of a miRNA to the target mRNA. As a result, translation of the target mRNA is inhibited and the mRNA may be destabilized. The inhibitory effects of miRNAs have been linked to diverse cellular processes including malignant proliferation, apoptosis, development, differentiation, and metabolic processes. We asked whether endogenous fluctuations in a set of mRNA and miRNA profiles contain correlated changes that are statistically distinguishable from the many other fluctuations in the data set. Methodology/Principal Findings. RNA was extracted from 12 human primary brain tumor biopsies. These samples were used to determine genome-wide mRN

Correlation of umbilical cord blood haematopoietic stem and progenitor cell levels with birth weight: implications for a prenatal influence on cancer risk

We examined the relation with birth weight and umbilical cord blood concentrations of haematopoietic stem and progenitor populations in 288 singleton infants. Across the whole range of birth weight, there was a positive relation between birth weight and CD34+CD38− cells, with each 500 g increase in birth weight being associated with a 15.5% higher (95% confidence interval: 1.6–31.3%) cell concentration. CD34+ and CD34+c-kit+ cells had J-shaped relations and CFU-GM cells had a U-shaped relation with birth weight. Among newborns with ⩾3000 g birth weights, concentrations of these cells increased with birth weight, while those below 3000 g had higher stem cell concentrations than the reference category of 3000–3499 g. Adjustment for cord blood plasma insulin-like growth factor-1 levels weakened the stem and progenitor cell–birth weight associations. The positive associations between birth weight and stem cell measurements for term newborns with a normal-to-high birth weight support the stem cell burden hypothesis of cancer risk

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Identification and characterisation of novel SNP markers in Atlantic cod: Evidence for directional selection

<p>Abstract</p> <p>Background</p> <p>The Atlantic cod (<it>Gadus morhua</it>) is a groundfish of great economic value in fisheries and an emerging species in aquaculture. Genetic markers are needed to identify wild stocks in order to ensure sustainable management, and for marker-assisted selection and pedigree determination in aquaculture. Here, we report on the development and evaluation of a large number of Single Nucleotide Polymorphism (SNP) markers from the alignment of Expressed Sequence Tag (EST) sequences in Atlantic cod. We also present basic population parameters of the SNPs in samples of North-East Arctic cod and Norwegian coastal cod obtained from three different localities, and test for SNPs that may have been targeted by natural selection.</p> <p>Results</p> <p>A total of 17,056 EST sequences were used to find 724 putative SNPs, from which 318 segregating SNPs were isolated. The SNPs were tested on Atlantic cod from four different sites, comprising both North-East Arctic cod (NEAC) and Norwegian coastal cod (NCC). The average heterozygosity of the SNPs was 0.25 and the average minor allele frequency was 0.18. <it>F</it>_{<it>ST </it>}values were highly variable, with the majority of SNPs displaying very little differentiation while others had <it>F</it>_{<it>ST </it>}values as high as 0.83. The <it>F</it>_{<it>ST </it>}values of 29 SNPs were found to be larger than expected under a strictly neutral model, suggesting that these loci are, or have been, influenced by natural selection. For the majority of these outlier SNPs, allele frequencies in a northern sample of NCC were intermediate between allele frequencies in a southern sample of NCC and a sample of NEAC, indicating a cline in allele frequencies similar to that found at the Pantophysin I locus.</p> <p>Conclusion</p> <p>The SNP markers presented here are powerful tools for future genetics work related to management and aquaculture. In particular, some SNPs exhibiting high levels of population divergence have potential to significantly enhance studies on the population structure of Atlantic cod.</p