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Author(s): Schneider, Claudio; Feller, Martin; Bauer, Douglas C; Collet, Tinh-Hai; da Costa, Bruno R; Auer, Reto; Peeters, Robin P; Brown, Suzanne J; Bremner, Alexandra P; O'Leary, Peter C; Feddema, Peter; Leedman, Peter J; Aujesky, Drahomir; Walsh, John P; Rodondi, Nicolas | Abstract: ObjectiveGuidelines for thyroid function evaluation recommend testing TSH first, then assessing fT4 only if TSH is out of the reference range (two-step), but many clinicians initially request both TSH and fT4 (one-step). Given limitations of previous studies, we aimed to compare the two-step with the one-step approach in an unselected community-dwelling study population, and develop a prediction score based on clinical parameters that could identify at-risk patients for thyroid dysfunction.DesignCross-sectional analysis of the population-based Busselton Health Study.MethodsWe compared the two-step with the one-step approach, focusing on cases that would be missed by the two-step approach, i.e. those with normal TSH, but out-of-range fT4. We used likelihood ratio tests to identify demographic and clinical parameters associated with thyroid dysfunction and developed a clinical prediction score by using a beta-coefficient based scoring method.ResultsFollowing the two-step approach, 93.0% of all 4471 participants had normal TSH and would not need further testing. The two-step approach would have missed 3.8% of all participants (169 of 4471) with a normal TSH, but a fT4 outside the reference range. In 85% (144 of 169) of these cases, fT4 fell within 2 pmol/l of fT4 reference range limits, consistent with healthy outliers. The clinical prediction score that performed best excluded only 22.5% of participants from TSH testing.ConclusionThe two-step approach may avoid measuring fT4 in as many as 93% of individuals with a very small risk of missing thyroid dysfunction. Our findings do not support the simultaneous initial measurement of both TSH and fT4.

Background: Atrial fibrillation (AF) is a highly prevalent disorder leading to heart failure, stroke, and death. Enhanced understanding of modifiable risk factors may yield opportunities for prevention. The risk of AF is increased in subclinical hyperthyroidism, but it is uncertain whether variations in thyroid function within the normal range or subclinical hypothyroidism are also associated with AF. Methods: We conducted a systematic review and obtained individual participant data from prospective cohort studies that measured thyroid function at baseline and assessed incident AF. Studies were identified from MEDLINE and EMBASE databases from inception to July 27, 2016. The euthyroid state was defined as thyroid-stimulating hormone (TSH) 0.45 to 4.49 mIU/L, and subclinical hypothyroidism as TSH 4.5 to 19.9 mIU/L with free thyroxine (fT4) levels within reference range. The association of TSH levels in the euthyroid and subclinical hypothyroid range with incident AF was examined by using Cox proportional hazards models. In euthyroid participants, we additionally examined the association between fT4 levels and incident AF. Results: Of 30 085 participants from 11 cohorts (278 955 person-years of follow-up), 1958 (6.5%) had subclinical hypothyroidism and 2574 individuals (8.6%) developed AF during follow-up. TSH at baseline was not significantly associated with incident AF in euthyroid participants or those with subclinical hypothyroidism. Higher fT4 levels at baseline in euthyroid individuals were associated with increased AF risk in age- and sex-adjusted analyses (hazard ratio, 1.45; 95% confidence interval, 1.26–1.66, for the highest quartile versus the lowest quartile of fT4; P for trend ≤0.001 across quartiles). Estimates did not substantially differ after further adjustment for preexisting cardiovascular disease. Conclusions: In euthyroid individuals, higher circulating fT4 levels, but not TSH levels, are associated with increased risk of incident AF.

Background: Graft right ventricular (RV) function is compromised directly posttransplant, especially in heart transplantation (HTx) recipients with pretransplant pulmonary hypertension (PH). Graft RV size and systolic function, and the effect of the recipient's pulmonary haemodynamics on the graft extracellular matrix are not well characterised in the patients long-term after HTx. Aim: Comparison of RV size and systolic function in HTx recipients' long-term posttransplant stratified by the presence of pretransplant PH. Methods: HTx survivors >/=2 years posttransplant were divided into group I without pretransplant PH (pulmonary vascular resistance, PVR /=2.5Wood units, n=16). RV size and systolic function were measured using cardiac magnetic resonance imaging (CMR). The collagen content was assessed in septal endomyocardial biopsies obtained at HTx and at study inclusion. Results: Mean posttransplant follow-up was 5.2+/-2.9 years (group I) and 4.9+/-2.2 years (group II) (p=0.70). PVR was 1.5+/-0.6 vs 4.1+/-1.7Wood units pretransplant (p/=0.07). Collagen content at transplantation and at follow-up were not different (p always >/=0.60). Conclusion: Posttransplant normalisation of pretransplant PH is associated with normal graft RV function long-term after HTx.

Fosfor je esencijalni makroelement koji je s poljoprivrednog gledišta izrazito bitan za sam rast i razvoj bilja gdje ima ulogu u energetskim reakcijama u biljci, fotosintezi, respriraciji te transferu gena i hraniva i stoga je cilj proučiti prostornu varijabilnost biljci pristupačnog fosfora kako bi se omogućila kvalitetna opskrbljenost u određenim uvjetima primjenom stečenog znanja. Nedostatak fosfora odražava se na čitav rast i razvoj biljke, odgađa cvatnju i zriobu što može stvoriti štete u proizvodnji dok se kod dobre opskrbljenosti povećava prinos. Vodotopljivi fosfati su najmanje zastupljena frakcija fosfora u tlu. U vodenoj fazi tla nalazi se u prosjeku manje od 1 kg ha-1 fosfora, dok porastom njihove koncentracije (nakon gnojidbe) dolazi do brze transformacije u manje topljive oblike. Ta kritična koncentracija ravnoteže vodotopivih i manje topivih oblika fosfora ovisi prije svega o količini fosfora koja se već nalazi u tlu. Utvrđivanje te vrijednosti značajan je zadatak agrokemije jer ona pokazuje razinu raspoloživog fosfora za ishranu bilja nakon gnojidbe fosforom, odnosno stupanj njegove efikasnosti. Na opskrbljenost pojedinog tipa tla fosforom utječu: mineralni sastav i fizikalna svojstva tla, količina gline, pH i temperatura, a u velikoj mjeri pridonosi i antropogeni utjecaj. U kiselijim tlima često se javlja manjak fosfora, kalija, kalcija, magnezija i mangana. Postoji velika potreba da se istraži prostorna varijabilnost fizikalnih svojstava tla preciznijim tehnikama kako bi se oplemenili i podržali različiti načini korištenja poljoprivrednog zemljišta. Fizikalna svojstva tla bitan su faktor u varijabilnosti količine hraniva u biljci pristupačnom obliku. Količina organske tvari u tlu također može utjecati na količinu pristupačnog fosfora. Najčešće korištena metoda utvrđivanja biljci pristupačnog fosfora u Hrvatskoj je AL-metoda. Za izražavanje prostornih obrazaca varijabli okoliša često se koristi geostatistika, a kriging, kao najpoznatija interpolacijska metoda, korišten je više desetljeća kao sinonim za geostatističku interpolaciju i dokazao se stabilnim za procjenu vrijednosti na neuzorkovanim mjestima obrađujući okolne uzorkovane podatke u određenoj shemi. Phosphorus is an essential macronutrient, and from the agricultural point of view is extremely important for the growth and development of plants where it has part in energetic reactions, photosynthesis, respiration and transfer of genes and nutrients. Therefore the objective is to study spatial variability of the plant available phosphorus to enable the good supply in various conditions, using the acquired knowledge. Phosphorus deficiency affects to overall growth and development of the plant and delays flowering and maturations which can cause production faults, while during good supply the yield grows. Water-soluble phosphates are at least represented fraction of phosphorus in the soil. In the aqueous phase of the soil there is an average quantity of less than 1 kg ha-1 of phosphorus, while by increasing concentration (after fertilization) it is quickly transformed in less soluble forms. That critical concentration of water-soluble and less-soluble equilibrium especially depends on amount that is already in the soil. Definition of that amount is an important mission for agrochemistry because it shows the level of available phosphorus for plant nutrition after the fertilization or level of its efficiency. Factors of phosphorus supply in soils are: mineral composition, physical characteristics, amount of clay, pH and temperature, but there is also a large influence of humans. In acidic soils there is a lack of phosphorus, potassium, magnesium and manganese. There is a great need of exploration of physical characteristics spatial variability with more precise techniques to refine and support different ways of farmland usage. Physical characteristics are important factor that influences on amount of available phosphorus. Most common method of plant available phosphorus measurement in Croatia is an AL-method. Geostatistics is often used for representation of spatial patterns of environmental variables, and kriging, as the most famous interpolation method, has been used for decades as a synonym for geostatistic interpolation and was proved as stable for estimation of values of unsampled spots by processing the sampled data in determined pattern.

BACKGROUND: Previous studies on childhood cancer and nuclear power plants (NPPs) produced conflicting results. We used a cohort approach to examine whether residence near NPPs was associated with leukaemia or any childhood cancer in Switzerland. METHODS: We computed person-years at risk for children aged 0-15 years born in Switzerland from 1985 to 2009, based on the Swiss censuses 1990 and 2000 and identified cancer cases from the Swiss Childhood Cancer Registry. We geo-coded place of residence at birth and calculated incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing the risk of cancer in children born 15 km away, using Poisson regression models. RESULTS: We included 2925 children diagnosed with cancer during 21 117 524 person-years of follow-up; 953 (32.6%) had leukaemia. Eight and 12 children diagnosed with leukaemia at ages 0-4 and 0-15 years, and 18 and 31 children diagnosed with any cancer were born 15 km away, the IRRs (95% CI) for leukaemia in 0-4 and 0-15 year olds were 1.20 (0.60-2.41) and 1.05 (0.60-1.86), respectively. For any cancer, corresponding IRRs were 0.97 (0.61-1.54) and 0.89 (0.63-1.27). There was no evidence of a dose-response relationship with distance (P > 0.30). Results were similar for residence at diagnosis and at birth, and when adjusted for potential confounders. Results from sensitivity analyses were consistent with main results. CONCLUSIONS: This nationwide cohort study found little evidence of an association between residence near NPPs and the risk of leukaemia or any childhood cancer.

Previous studies demonstrated that impaired left ventricular (LV) relaxation in cardiac allografts limits exercise tolerance post-transplant despite preserved systolic ejection fraction (EF). This study tested in human cardiac allografts whether the isovolumic relaxation time (IVRT), which provides the basis for most of diastolic LV filling, relates with gene expression of regulatory proteins of calcium homeostasis or cardiac matrix proteins. Gene expression was studied in 31 heart transplant recipients (25 male, 6 female) 13-83 months post-transplant with LVEF >50%, LV end-diastolic pressure

Biomedical research increasingly depends on access to and analysis of distributed medical and biomedical data. In biomedical research, datasets are often collected at multiple locations, as it is difficult to recruit required patient populations at one location. The sensitive nature of these datasets leads to a need for secure sharing methods that can work with distributed databases and image archives. The efficient implementation of such methods is complicated by the fact that the researchers who need to access data are often behind firewalls that prohibit inbound connections. This restriction, combined with large data volumes and many small files, leads to significant data transfer challenges. We present a data management framework suitable for such distributed biomedical research environments and describe its application in the context of FBIRN, a distributed data-sharing system for medical researchers. The framework includes security tools, catalogs for managing datasets, and a secure data transfer service.

Background. We investigated the effectiveness of long-term antibiotic treatment in patients with Crohn's disease. Methods. We performed a systematic review and meta-analysis of randomized clinical trials. Data sources were Medline (from 1966 through June 2009), EMBASE (from 1980 through June 2009), Cochrane Central Register of Controlled Trials (issue 3, 2009), and references from relevant publications. Trials that compared antibiotic therapy during at least 3 months with placebo were included. Outcomes were remission in patients with active disease and relapse in patients with inactive disease. Results from intention-to-treat analyses were combined in a random-effects meta-analysis, stratified by class of drug. Odds ratios (ORs) >1 indicate superiority of antibacterial treatment over placebo. Numbers needed to treat for 1 year to keep 1 additional patient in remission were calculated. Results. Sixteen trials that examined 13 treatment regimens in 865 patients were included in the meta-analysis. The median duration of treatment was 6 months (range, 3-24 months). Three trials of nitroimidazoles showed benefit, with a combined OR of 3.54 (95% confidence interval [CI], 1.94-6.47). Similarly, the combined OR from 4 trials of clofazimine was 2.86 (95% CI, 1.67-4.88). For patients with active disease, the number needed to treat was 3.4 (95% CI, 2.3-7.0) for nitroimidazoles and 4.2 (95% CI, 2.7-9.3) for clofazimine. The corresponding numbers needed to treat for inactive disease were 6.1 (95% CI, 5.0-9.7) and 6.9 (95% CI, 5.4-12.0). No benefit was evident for classic drugs against tuberculosis (3 trials; OR, 0.58; 95% CI, 0.29-1.18). Results for clarithromycin were heterogeneous (I2=77%; P=.005) and not combined in the meta-analysis. Conclusions. Long-term treatment with nitroimidazoles or clofazimine appears to be effective in patients with Crohn's disease

BackgroundTo date, few risk factors for childhood acute lymphoblastic leukemia (ALL) have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL).Methodology/principal findingsIn this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004), remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060) after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032) and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141) and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019), with some evidence for an effect modification (p-value for interaction = 0.040).ConclusionsAs in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

BACKGROUND: Exercise capacity after heart transplantation (HTx) remains limited despite normal left ventricular systolic function of the allograft. Various clinical and haemodynamic parameters are predictive of exercise capacity following HTx. However, the predictive significance of chronotropic competence has not been demonstrated unequivocally despite its immediate relevance for cardiac output. AIMS: This study assesses the predictive value of various clinical and haemodynamic parameters for exercise capacity in HTx recipients with complete chronotropic competence evolving within the first 6 postoperative months. METHODS: 51 patients were enrolled in this exercise study. Patients were included when at least >6 months after HTx and without negative chronotropic medication or factors limiting exercise capacity such as significant transplant vasculopathy or allograft rejection. Clinical parameters were obtained by chart review, haemodynamic parameters from current cardiac catheterisation, and exercise capacity was assessed by treadmill stress testing. A stepwise multiple regression model analysed the proportion of the variance explained by the predictive parameters. RESULTS: The mean age of these 51 HTx recipients was 55.4 +/- 13.2 yrs on inclusion, 42 pts were male and the mean time interval after cardiac transplantation was 5.1 +/- 2.8 yrs. Five independent predictors explained 47.5% of the variance observed for peak exercise capacity (adjusted R2 = 0.475). In detail, heart rate response explained 31.6%, male gender 5.2%, age 4.1%, pulmonary vascular resistance 3.7%, and body-mass index 2.9%. CONCLUSION: Heart rate response is one of the most important predictors of exercise capacity in HTx recipients with complete chronotropic competence and without relevant transplant vasculopathy or acute allograft rejection.

Summary This systematic review assesses the evidence for an association between Mycobacterium avium subspecies paratuberculosis (MAP) and Crohn's disease. We analysed 28 case-control studies comparing MAP in patients with Crohn's disease with individuals free of inflammatory bowel disease (IBD) or patients with ulcerative colitis. Compared with individuals free of IBD, the pooled odds ratio (OR) from studies using PCR in tissue samples was 7·01 (95% CI 3·95–12·4) and was 1·72 (1·02–2·90) in studies using ELISA in serum. ORs were similar for comparisons with ulcerative colitis patients (PCR, 4·13 [1·57–10·9]; ELISA, 1·88 [1·26–2·81]). The association of MAP with Crohn's disease seems to be specific, but its role in the aetiology of Crohn's disease remains to be defined.

Carcinoma originating in the renal pelvis or calyces may invade the renal parenchyma extensively. The resultant parenchymal component may become the dominant feature of the neoplasm, obscuring the source and nature of the original lesion. It appears, however, that these tumors alter the renal vascular pattern in characteristic fashion so that selective renal angiography is helpful in establishing the correct diagnosis. The vascular changes are different and more subtle than those associated with hypernephromas. It is important that neoplasm not be excluded from consideration because of the absence of bizarre tumor vessel formation. It is the purpose of this paper to describe the changes associated with carcinomas arising from the renal pelvis and calyceal system that have infiltrated the renal parenchyma. We have had the opportunity to study 4 such cases, 3 of the transitional-cell type and 1 of the squamous-cell variety. All showed similar arteriographic findings. Roentgen Features These tumors arise fro...

Oxidative stress can contribute to the development of diseases, and may originate from exposures to toxicants commonly found in air pollution and cigarette smoke such as polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). Yet, associations between these exposures and oxidative stress biomarkers are poorly characterized. We report here novel associations between 14 exposure biomarkers of PAHs and VOCs, and two oxidative stress biomarkers; 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-isoprostaglandin F 2α (8-isoprostane) in urine obtained from smokers participating in an ongoing clinical study (ESTxENDS, NCT03589989). We also assessed associations between six biomarkers of tobacco smoke exposure (metabolites of nicotine and tobacco-specific nitrosamines (TSNAs)) and both oxidative stress biomarkers. We then quantified the relative importance of each family of the 20 exposure biomarkers on oxidative stress. Participating smokers (153 men and 117 women, median age 44 years) had on average smoked 25 [2-62] years and smoked about 17 [5-40] cigarettes per day at the time of the study. Multiple linear regression results showed an association between 8-oxodG concentrations and the following metabolites in decreasing relative importance: PAHs (beta coefficient β = 0.105, p-value 2 = 0.15) > VOCs (β = 0.028, p < 0.001, partial R 2 = 0.09) > nicotine (β = 0.226, p < 0.001, partial R 2 = 0.08); and between 8-isoprostane concentrations and metabolites of PAHs (β = 0.117, p < 0.001, partial R 2 = 0.14) > VOCs (β = 0.040, p < 0.001, partial R 2 = 0.14) > TSNAs (β = 0.202, p = 0.003, partial R 2 = 0.09) > nicotine (β = 0.266, p < 0.001, partial R 2 = 0.08). Behavioral factors known to contribute to oxidative stress, including sleep quality, physical activity, and alcohol consumption, did not play a significant role. Exposures to PAHs and VOCs among smokers were significantly associated with oxidative stress.