Showing papers by "University of Southern Denmark published in 2012"
••
TL;DR: In this paper, the authors describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years-old) from 105 countries.
4,373 citations
••
University of Melbourne1, Singapore National Eye Center2, Allergan3, Aarhus University4, National Yang-Ming University5, University of London6, University of Southern Denmark7, Colorado School of Public Health8, Erasmus University Rotterdam9, Yamagata University10, University of Wisconsin-Madison11, L V Prasad Eye Institute12, University of Warwick13, University of Pittsburgh14, University of Turin15, Madras Medical College16, Rutgers University17, The Heart Research Institute18, Johns Hopkins University19, University of Southern California20, University of Sydney21, Capital Medical University22, Kyushu University23, Centers for Disease Control and Prevention24, National University of Singapore25
TL;DR: Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR, and these data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence.
Abstract: OBJECTIVE To examine the global prevalence and major risk factors for diabetic retinopathy (DR) and vision-threatening diabetic retinopathy (VTDR) among people with diabetes. RESEARCH DESIGN AND METHODS A pooled analysis using individual participant data from population-based studies around the world was performed. A systematic literature review was conducted to identify all population-based studies in general populations or individuals with diabetes who had ascertained DR from retinal photographs. Studies provided data for DR end points, including any DR, proliferative DR, diabetic macular edema, and VTDR, and also major systemic risk factors. Pooled prevalence estimates were directly age-standardized to the 2010 World Diabetes Population aged 20–79 years. RESULTS A total of 35 studies (1980–2008) provided data from 22,896 individuals with diabetes. The overall prevalence was 34.6% (95% CI 34.5–34.8) for any DR, 6.96% (6.87–7.04) for proliferative DR, 6.81% (6.74–6.89) for diabetic macular edema, and 10.2% (10.1–10.3) for VTDR. All DR prevalence end points increased with diabetes duration, hemoglobin A 1c , and blood pressure levels and were higher in people with type 1 compared with type 2 diabetes. CONCLUSIONS There are approximately 93 million people with DR, 17 million with proliferative DR, 21 million with diabetic macular edema, and 28 million with VTDR worldwide. Longer diabetes duration and poorer glycemic and blood pressure control are strongly associated with DR. These data highlight the substantial worldwide public health burden of DR and the importance of modifiable risk factors in its occurrence. This study is limited by data pooled from studies at different time points, with different methodologies and population characteristics.
3,282 citations
••
TL;DR: Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer's acetate.
Abstract: A B S T R AC T Background Hydroxyethyl starch (HES) is widely used for fluid resuscitation in intensive care units (ICUs), but its safety and efficacy have not been established in patients with severe sepsis. Methods In this multicenter, parallel-group, blinded trial, we randomly assigned patients with severe sepsis to fluid resuscitation in the ICU with either 6% HES 130/0.42 (Tetraspan) or Ringer’s acetate at a dose of up to 33 ml per kilogram of ideal body weight per day. The primary outcome measure was either death or end-stage kidney failure (dependence on dialysis) at 90 days after randomization. RESULTS Of the 804 patients who underwent randomization, 798 were included in the modi fied intention-to-treat population. The two intervention groups had similar baseline characteristics. At 90 days after randomization, 201 of 398 patients (51%) assigned to HES 130/0.42 had died, as compared with 172 of 400 patients (43%) assigned to Ringer’s acetate (relative risk, 1.17; 95% confidence interval [CI], 1.01 to 1.36; P = 0.03); 1 patient in each group had end-stage kidney failure. In the 90-day period, 87 patients (22%) assigned to HES 130/0.42 were treated with renal-replacement therapy versus 65 patients (16%) assigned to Ringer’s acetate (relative risk, 1.35; 95% CI, 1.01 to 1.80; P = 0.04), and 38 patients (10%) and 25 patients (6%), respectively, had severe bleeding (relative risk, 1.52; 95% CI, 0.94 to 2.48; P = 0.09). The results were supported by multivariate analyses, with adjustment for known risk factors for death or acute kidney injury at baseline. CONCLUSIONS Patients with severe sepsis assigned to fluid resuscitation with HES 130/0.42 had an increased risk of death at day 90 and were more likely to require renal-replacement therapy, as compared with those receiving Ringer’s acetate. (Funded by the Danish Research Council and others; 6S ClinicalTrials.gov number, NCT00962156.)
1,500 citations
••
Karol Estrada1, Unnur Styrkarsdottir, Evangelos Evangelou2, Yi-Hsiang Hsu3 +187 more•Institutions (69)
TL;DR: Light is shed on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility and within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways.
Abstract: Bone mineral density (BMD) is the most widely used predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and east Asian ancestry. We tested the top BMD-associated markers for replication in 50,933 independent subjects and for association with risk of low-trauma fracture in 31,016 individuals with a history of fracture (cases) and 102,444 controls. We identified 56 loci (32 new) associated with BMD at genome-wide significance (P < 5 × 10(-8)). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal stem cell differentiation, endochondral ossification and Wnt signaling pathways. However, we also discovered loci that were localized to genes not known to have a role in bone biology. Fourteen BMD-associated loci were also associated with fracture risk (P < 5 × 10(-4), Bonferroni corrected), of which six reached P < 5 × 10(-8), including at 18p11.21 (FAM210A), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
1,076 citations
••
TL;DR: Due to high permittivity, the magnetic dipole resonance is observed in the visible spectral range for Si nanoparticles with diameters of ∼200 nm, thereby opening a way to the realization of isotropic optical metamaterials with strong magnetic responses in thevisible region.
Abstract: Strong resonant light scattering by individual spherical Si nanoparticles is experimentally demonstrated, revealing pronounced resonances associated with the excitation of magnetic and electric modes in these nanoparticles. It is shown that the low-frequency resonance corresponds to the magnetic dipole excitation. Due to high permittivity, the magnetic dipole resonance is observed in the visible spectral range for Si nanoparticles with diameters of ∼200 nm, thereby opening a way to the realization of isotropic optical metamaterials with strong magnetic responses in the visible region.
932 citations
••
TL;DR: Cardiolipin content followed by citrate synthase activity and complex I activity were the biomarkers showing the strongest association with mitochondrial content, and mtDNA was found to be a poor biomarker of mitochondrial content.
Abstract: Skeletal muscle mitochondrial content varies extensively between human subjects. Biochemical measures of mitochondrial proteins, enzyme activities and lipids are often used as markers of mitochondrial content and muscle oxidative capacity (OXPHOS). The purpose of this study was to determine how closely associated these commonly used biochemical measures are to muscle mitochondrial content and OXPHOS. Sixteen young healthy male subjects were recruited for this study. Subjects completed a graded exercise test to determine maximal oxygen uptake (VO2peak) and muscle biopsies were obtained from the vastus lateralis. Mitochondrial content was determined using transmission electron microscopy imaging and OXPHOS was determined as the maximal coupled respiration in permeabilized fibres. Biomarkers of interest were citrate synthase (CS) activity, cardiolipin content, mitochondrial DNA content (mtDNA), complex I–V protein content, and complex I–IV activity. Spearman correlation coefficient tests and Lin's concordance tests were applied to assess the absolute and relative association between the markers and mitochondrial content or OXPHOS. Subjects had a large range of VO2peak (range 29.9–71.6ml min−1 kg−1) and mitochondrial content (4–15% of cell volume).Cardiolipin content showed the strongest association with mitochondrial content followed by CS and complex I activities. mtDNA was not related to mitochondrial content. Complex IV activity showed the strongest association with muscle oxidative capacity followed by complex II activity.We conclude that cardiolipin content, and CS and complex I activities are the biomarkers that exhibit the strongest association with mitochondrial content, while complex IV activity is strongly associated with OXPHOS capacity in human skeletal muscle.
919 citations
••
TL;DR: Recommendations include creation and improvement of access to places for physical activity with informational outreach activities, community-scale and street-scale urban design and land use, active transport policy and practices, and community-wide policies and planning.
833 citations
••
Alisa K. Manning1, Alisa K. Manning2, Alisa K. Manning3, Robert A. Scott +240 more•Institutions (69)
TL;DR: Six previously unknown loci associated with fasting insulin at P < 5 × 10−8 in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals are presented.
Abstract: Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and β-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 × 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
811 citations
••
TL;DR: The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years, and endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for ostrogens receptor-negative disease and for lobular than for ductal tumours.
Abstract: BACKGROUND:Menarche and menopause mark the onset and cessation, respectively, of ovarian activity associated with reproduction, and affect breast cancer risk. Our aim was to assess the strengths of their effects and determine whether they depend on characteristics of the tumours or the affected women.METHODS:Individual data from 117 epidemiological studies, including 118 964 women with invasive breast cancer and 306 091 without the disease, none of whom had used menopausal hormone therapy, were included in the analyses. We calculated adjusted relative risks (RRs) associated with menarche and menopause for breast cancer overall, and by tumour histology and by oestrogen receptor expression.FINDINGS:Breast cancer risk increased by a factor of 1·050 (95% CI 1·044-1·057; p<0·0001) for every year younger at menarche, and independently by a smaller amount (1·029, 1·025-1·032; p<0·0001), for every year older at menopause. Premenopausal women had a greater risk of breast cancer than postmenopausal women of an identical age (RR at age 45-54 years 1·43, 1·33-1·52, p<0·001). All three of these associations were attenuated by increasing adiposity among postmenopausal women, but did not vary materially by women's year of birth, ethnic origin, childbearing history, smoking, alcohol consumption, or hormonal contraceptive use. All three associations were stronger for lobular than for ductal tumours (p<0·006 for each comparison). The effect of menopause in women of an identical age and trends by age at menopause were stronger for oestrogen receptor-positive disease than for oestrogen receptor-negative disease (p<0·01 for both comparisons).INTERPRETATION:The effects of menarche and menopause on breast cancer risk might not be acting merely by lengthening women's total number of reproductive years. Endogenous ovarian hormones are more relevant for oestrogen receptor-positive disease than for oestrogen receptor-negative disease and for lobular than for ductal tumours.
759 citations
••
TL;DR: Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
Abstract: Aims Patients with chest pain and no obstructive coronary artery disease (CAD) are considered at low risk for cardiovascular events but evidence supporting this is scarce. We investigated the prognostic implications of stable angina pectoris in relation to the presence and degree of CAD with no obstructive CAD in focus.
Methods and results We identified 11 223 patients referred for coronary angiography (CAG) in 1998–2009 with stable angina pectoris as indication and 5705 participants from the Copenhagen City Heart Study for comparison. Main outcome measures were major adverse cardiovascular events (MACE), defined as cardiovascular death, myocardial infarction, stroke or heart failure, and all-cause mortality. Significantly more women (65%) than men (32%) had no obstructive CAD ( P < 0.001). In Cox's models adjusted for age, body mass index, diabetes, smoking, and use of lipid-lowering or antihypertensive medication, hazard ratios (HRs) associated with no obstructive CAD were similar in men and women. In the pooled analysis, the risk of MACE increased with increasing degrees of CAD with multivariable-adjusted HRs of 1.52 (95% confidence interval, 1.27–1.83) for patients with normal coronary arteries and 1.85 (1.51–2.28) for patients with diffuse non-obstructive CAD compared with the reference population. For all-cause mortality, normal coronary arteries and diffuse non-obstructive CAD were associated with HRs of 1.29 (1.07–1.56) and 1.52 (1.24–1.88), respectively.
Conclusion Patients with stable angina and normal coronary arteries or diffuse non-obstructive CAD have elevated risks of MACE and all-cause mortality compared with a reference population without ischaemic heart disease.
665 citations
••
TL;DR: It is concluded that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages.
Abstract: This White Paper highlights the developmental period as a plastic phase, which allows the organism to adapt to changes in the environment to maintain or improve reproductive capability in part through sustained health. Plasticity is more prominent prenatally and during early postnatal life, i.e., during the time of cell differentiation and specific tissue formation. These developmental periods are highly sensitive to environmental factors, such as nutrients, environmental chemicals, drugs, infections and other stressors. Nutrient and toxicant effects share many of the same characteristics and reflect two sides of the same coin. In both cases, alterations in physiological functions can be induced and may lead to the development of non-communicable conditions. Many of the major diseases – and dysfunctions – that have increased substantially in prevalence over the last 40 years seem to be related in part to developmental factors associated with either nutritional imbalance or exposures to environmental chemicals. The Developmental Origins of Health and Disease (DOHaD) concept provides significant insight into new strategies for research and disease prevention and is sufficiently robust and repeatable across species, including humans, to require a policy and public health response. This White Paper therefore concludes that, as early development (in utero and during the first years of postnatal life) is particularly sensitive to developmental disruption by nutritional factors or environmental chemical exposures, with potentially adverse consequences for health later in life, both research and disease prevention strategies should focus more on these vulnerable life stages.
••
TL;DR: The immunohistochemical DHS defined a large subset of DLBCLs with double-hit biology and was strongly associated with poor outcome in patients treated with R-CHOP.
Abstract: Purpose Approximately 5% of diffuse large B-cell lymphomas (DLBCLs) are double-hit lymphomas (DHLs) with translocations of both MYC and BCL2. DHLs are characterized by poor outcome. We tested whether DLBCLs with high expression of MYC protein and BCL2 protein share the clinical features and poor prognosis of DHLs. Patients and Methods Paraffin-embedded lymphoma samples from 193 patients with de novo DLBCL who were uniformly treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were studied using immunohistochemistry for MYC, BCL2, CD10, BCL6, and MUM1/interferon regulatory factor 4, and fluorescent in situ hybridization (FISH) for MYC and BCL2. Results FISH analysis identified DHL in 6% of patients, who showed the expected poor overall survival (OS; P = .002). On the basis of immunohistochemical MYC and BCL2 expression, a double-hit score (DHS) was assigned to all patients with DLBCL. The DHS-2 group, defined by high expression of both MYC and BCL2 protein, comprised ...
••
TL;DR: It is shown that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)] and selected XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity for Darwinian evolution and folding into defined structures.
Abstract: Genetic information storage and processing rely on just two polymers, DNA and RNA, yet whether their role reflects evolutionary history or fundamental functional constraints is currently unknown. With the use of polymerase evolution and design, we show that genetic information can be stored in and recovered from six alternative genetic polymers based on simple nucleic acid architectures not found in nature [xeno-nucleic acids (XNAs)]. We also select XNA aptamers, which bind their targets with high affinity and specificity, demonstrating that beyond heredity, specific XNAs have the capacity for Darwinian evolution and folding into defined structures. Thus, heredity and evolution, two hallmarks of life, are not limited to DNA and RNA but are likely to be emergent properties of polymers capable of information storage.
••
TL;DR: The fact that TNF and IL-1, and suppossedly also IL-6, are produced by microglia within the therapeutic window place these cells centrally in potential future stroke therapy, in the context of suggestions that neuronal sensitivity to ischemia may be modulated by cytokines.
Abstract: Inflammation is a hallmark of stroke pathology. The cytokines, tumor necrosis factor (TNF), interleukin (IL)-1, and IL-6, modulate tissue injury in experimental stroke and are therefore potential targets in future stroke therapy. The effect of these cytokines on infarct evolution depends on their availability in the ischemic penumbra in the early phase after stroke onset, corresponding to the therapeutic window (<4.5 hours), which is similar in human and experimental stroke. This review summarizes a large body of literature on the spatiotemporal and cellular production of TNF, IL-1, and IL-6, focusing on the early phase in experimental and human stroke. We also review studies of cytokines in blood and cerebrospinal fluid in stroke. Tumor necrosis factor and IL-1 are upregulated early in peri-infarct microglia. Newer literature suggests that IL-6 is produced by microglia, in addition to neurons. Tumor necrosis factor- and IL-1-producing macrophages infiltrate the infarct and peri-infarct with a delay. This information is discussed in the context of suggestions that neuronal sensitivity to ischemia may be modulated by cytokines. The fact that TNF and IL-1, and suppossedly also IL-6, are produced by microglia within the therapeutic window place these cells centrally in potential future stroke therapy.
••
Icahn School of Medicine at Mount Sinai1, Erasmus University Rotterdam2, University of Southern Denmark3, University of California, Davis4, University of North Carolina at Chapel Hill5, University of Groningen6, Charité7, University of Geneva8, University of Pennsylvania9, Hannover Medical School10, Pennsylvania State University11
TL;DR: This research presents a novel and scalable approach to regenerative medicine that addresses the underlying cause of childhood obesity, which is known as “chronic disease of the immune system”.
Abstract: Hugh A. Sampson, MD, Roy Gerth van Wijk, MD, Carsten Bindslev-Jensen, MD, PhD, Scott Sicherer, MD, Suzanne S. Teuber, MD, A. Wesley Burks, MD, Anthony E. J. Dubois, MD, Kirsten Beyer, MD, Philippe A. Eigenmann, MD, Jonathan M. Spergel, MD, PhD, Thomas Werfel, MD, and Vernon M. Chinchilli, PhD New York, NY, Rotterdam and Groningen, The Netherlands, Odense, Denmark, Davis, Calif, Chapel Hill, NC, Berlin and Hannover, Germany, Geneva, Switzerland, and Philadelphia and Hershey, Pa
••
University of Cambridge1, University of Toronto2, University of Pennsylvania3, University of Southampton4, University of Helsinki5, University of Southern California6, QIMR Berghofer Medical Research Institute7, Columbia University8, National Institutes of Health9, Mayo Clinic10, Leipzig University11, Claude Bernard University Lyon 112, University of Melbourne13, University of Utah14, Cancer Prevention Institute of California15, Vilnius University16, University of Latvia17, University of Copenhagen18, Complutense University of Madrid19, University of Turin20, University of Florence21, Sapienza University of Rome22, German Cancer Research Center23, Memorial Hospital of South Bend24, Erasmus University Rotterdam25, Utrecht University26, Royal Devon and Exeter Hospital27, Churchill Hospital28, University Hospital of Wales29, University College London30, Fox Chase Cancer Center31, University of Kansas32, University of Cologne33, Technische Universität München34, Dresden University of Technology35, University of Kiel36, University of Düsseldorf37, Heidelberg University38, University of Ulm39, Hannover Medical School40, University of Münster41, Charité42, University of Würzburg43, University of Paris44, Georgetown University45, Laval University46, University of Padua47, Peter MacCallum Cancer Centre48, University of Chicago49, Harvard University50, University of Delaware51, American Cancer Society52, Medical University of Vienna53, Ohio State University54, University of Southern Denmark55, University of Pisa56, Karolinska Institutet57, Lund University58, City of Hope National Medical Center59, University of California, San Francisco60, Roswell Park Cancer Institute61, Cedars-Sinai Medical Center62
TL;DR: Pathologic characteristics of BRCA1 and BRCa2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis.
Abstract: BACKGROUND: Previously, small studies have found that BRCA1 and BRCA2 breast tumors differ in their pathology. Analysis of larger datasets of mutation carriers should allow further tumor characterization.METHODS: We used data from 4,325 BRCA1 and 2,568 BRCA2 mutation carriers to analyze the pathology of invasive breast, ovarian, and contralateral breast cancers.RESULTS: There was strong evidence that the proportion of estrogen receptor (ER)-negative breast tumors decreased with age at diagnosis among BRCA1 (P-trend = 1.2 × 10(-5)), but increased with age at diagnosis among BRCA2, carriers (P-trend = 6.8 × 10(-6)). The proportion of triple-negative tumors decreased with age at diagnosis in BRCA1 carriers but increased with age at diagnosis of BRCA2 carriers. In both BRCA1 and BRCA2 carriers, ER-negative tumors were of higher histologic grade than ER-positive tumors (grade 3 vs. grade 1; P = 1.2 × 10(-13) for BRCA1 and P = 0.001 for BRCA2). ER and progesterone receptor (PR) expression were independently associated with mutation carrier status [ER-positive odds ratio (OR) for BRCA2 = 9.4, 95% CI: 7.0-12.6 and PR-positive OR = 1.7, 95% CI: 1.3-2.3, under joint analysis]. Lobular tumors were more likely to be BRCA2-related (OR for BRCA2 = 3.3, 95% CI: 2.4-4.4; P = 4.4 × 10(-14)), and medullary tumors BRCA1-related (OR for BRCA2 = 0.25, 95% CI: 0.18-0.35; P = 2.3 × 10(-15)). ER-status of the first breast cancer was predictive of ER-status of asynchronous contralateral breast cancer (P = 0.0004 for BRCA1; P = 0.002 for BRCA2). There were no significant differences in ovarian cancer morphology between BRCA1 and BRCA2 carriers (serous: 67%; mucinous: 1%; endometrioid: 12%; clear-cell: 2%).Conclusions/Impact: Pathologic characteristics of BRCA1 and BRCA2 tumors may be useful for improving risk-prediction algorithms and informing clinical strategies for screening and prophylaxis. Cancer Epidemiol Biomarkers Prev; 1-14. ©2011 AACR.
••
TL;DR: Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years.
Abstract: Context Perfluorinated compounds (PFCs) have emerged as important food contaminants They cause immune suppression in a rodent model at serum concentrations similar to those occurring in the US population, but adverse health effects of PFC exposure are poorly understood Objective To determine whether PFC exposure is associated with antibody response to childhood vaccinations Design, Setting, and Participants Prospective study of a birth cohort from the National Hospital in the Faroe Islands A total of 656 consecutive singleton births were recruited during 1997-2000, and 587 participated in follow-up through 2008 Main Outcome Measures Serum antibody concentrations against tetanus and diphtheria toxoids at ages 5 and 7 years Results Similar to results of prior studies in the United States, the PFCs with the highest serum concentrations were perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) Among PFCs in maternal pregnancy serum, PFOS showed the strongest negative correlations with antibody concentrations at age 5 years, for which a 2-fold greater concentration of exposure was associated with a difference of −39% (95% CI, −55% to −17%) in the diphtheria antibody concentration PFCs in the child's serum at age 5 years showed uniformly negative associations with antibody levels, especially at age 7 years, except that the tetanus antibody level following PFOS exposure was not statistically significant In a structural equation model, a 2-fold greater concentration of major PFCs in child serum was associated with a difference of −49% (95% CI, −67% to −23%) in the overall antibody concentration A 2-fold increase in PFOS and PFOA concentrations at age 5 years was associated with odds ratios between 238 (95% CI, 089 to 635) and 420 (95% CI, 154 to 1144) for falling below a clinically protective level of 01 IU/mL for tetanus and diphtheria antibodies at age 7 years Conclusion Elevated exposures to PFCs were associated with reduced humoral immune response to routine childhood immunizations in children aged 5 and 7 years
••
Ludwig Maximilian University of Munich1, German Red Cross2, Semmelweis University3, Cambridge University Hospitals NHS Foundation Trust4, University of Southern Denmark5, Leiden University6, Boston Children's Hospital7, University of Paris8, University of Naples Federico II9, University of Geneva10, Vrije Universiteit Brussel11
TL;DR: This guideline provides recommendations for the diagnosis and management of suspected cow's-milk protein allergy (CMPA) in Europe and presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA.
Abstract: Objectives: This guideline provides recommendations for the diagnosis and management of suspected cow’s-milk protein allergy (CMPA) in Europe. It presents a practical approach with a diagnostic algorithm and is based on recently published evidence-based guidelines on CMPA. Diagnosis: If CMPA is suspected by history and examination, then strict allergen avoidance is initiated. In certain circumstances (eg, a clear history of immediate symptoms, a life-threatening reaction with a positive test for CMP–specific IgE), the diagnosis can be made without a milk challenge. In all other circumstances, a controlled oral food challenge (open or blind) under medical supervision is required to confirm or exclude the diagnosis of CMPA. Treatment: In breast-fed infants, the mother should start a strict CMPfree diet. Non–breast-fed infants with confirmed CMPA should receive an extensively hydrolyzed protein-based formula with proven efficacy in appropriate clinical trials; amino acids–based formulae are reserved for certain situations. Soy protein formula, if tolerated, is an option beyond 6 months of age. Nutritional counseling and regular monitoring of growth are mandatory in all age groups requiring CMP exclusion. Reevaluation: Patients should be reevaluated every 6 to 12 months to assess whether they have developed tolerance to CMP. This is achieved in >75% by 3 years of age and >90% by 6 years of age. Inappropriate or overly long dietary eliminations should be avoided. Such restrictions may impair the quality of life of both child and family, induce improper growth, and incur unnecessary health care costs.
••
Aarhus University Hospital1, Lund University2, University of Oslo3, University of Eastern Finland4, Uppsala University5, Karolinska Institutet6, University of Copenhagen7, University of Oulu8, Umeå University9, Norwegian University of Science and Technology10, University of Southern Denmark11, Aarhus University12
TL;DR: Dose-dense induction followed by HDT/ASCT was well tolerated and led to long-term PFS in 44% of treatment-naive patients with PTCL, which represents an encouraging outcome, particularly considering the high median age and adverse risk profile of the study population.
Abstract: Purpose Systemic peripheral T-cell lymphomas (PTCLs) respond poorly to conventional therapy. To evaluate the efficacy of a dose-dense approach consolidated by up-front high-dose chemotherapy (HDT) ...
••
TL;DR: A meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease identifies novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
Abstract: Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
••
TL;DR: Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
Abstract: Allergic rhinitis (AR) and asthma represent global health problems for all age groups. Asthma and rhinitis frequently coexist in the same subjects. Allergic Rhinitis and its Impact on Asthma (ARIA) was initiated during a World Health Organization workshop in 1999 (published in 2001). ARIA has reclassified AR as mild/moderate-severe and intermittent/persistent. This classification closely reflects patients' needs and underlines the close relationship between rhinitis and asthma. Patients, clinicians, and other health care professionals are confronted with various treatment choices for the management of AR. This contributes to considerable variation in clinical practice, and worldwide, patients, clinicians, and other health care professionals are faced with uncertainty about the relative merits and downsides of the various treatment options. In its 2010 Revision, ARIA developed clinical practice guidelines for the management of AR and asthma comorbidities based on the Grading of Recommendation, Assessment, Development and Evaluation (GRADE) system. ARIA is disseminated and implemented in more than 50 countries of the world. Ten years after the publication of the ARIA World Health Organization workshop report, it is important to make a summary of its achievements and identify the still unmet clinical, research, and implementation needs to strengthen the 2011 European Union Priority on allergy and asthma in children.
••
Queen's University Belfast1, University of Pécs2, University of Düsseldorf3, Charles University in Prague4, Boston Children's Hospital5, Medical University of Vienna6, University of Leeds7, University of Oslo8, University of Copenhagen9, University of Bristol10, Medical University of Silesia11, University of Health Science12, Dresden University of Technology13, University of Southern Denmark14, Umeå University15
TL;DR: The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3–4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers.
Abstract: Aims/hypothesis
The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989–1998) and second (1999–2008) halves of the period.
••
TL;DR: Detailed Cu 2p, Cu LVV, O 1s and O KLL spectra are reported which are in good agreement with previous results and are mainly due to modifications of the 3d and O 2p electron configurations.
Abstract: The electronic and optical properties of Cu, CuO and Cu(2)O were studied by x-ray photoelectron spectroscopy (XPS) and reflection electron energy-loss spectroscopy (REELS). We report detailed Cu 2p, Cu LVV, O 1s and O KLL spectra which are in good agreement with previous results. REELS spectra, recorded for primary energies in the range from 150 to 2000 eV, were corrected for multiple inelastically scattered electrons to determine the effective inelastic scattering cross section. The dielectric functions and optical properties were determined by comparing the experimental inelastic electron scattering cross section with a simulated cross section calculated within the semi-classical dielectric response model in which the only input is Im(-1/e) by using the QUEELS-e(k,ω)-REELS software package. By Kramers-Kronig transformation of the determined Im(-1/e), the real and imaginary parts (e(1) and e(2)) of the dielectric function, and the refractive index n and extinction coefficient k were determined for Cu, CuO, and Cu(2)O in the 0-100 eV energy range. Observed differences between Cu, CuO and Cu(2)O are mainly due to modifications of the 3d and O 2p electron configurations.
••
TL;DR: The function, regulation, and mechanism of the different PPAR subtypes are reviewed with special emphasis on their role in the regulation of lipid metabolism.
••
TL;DR: General practice in Denmark is embedded in a universal tax-funded health care system in which GP and hospital services are free at the point of use and has shown an ability to adapt flexibly to new challenges.
Abstract: General practice is the corner stone of Danish primary health care. General practitioners (GPs) are similar to family physicians in the United States. On average, all Danes have 6.9 contacts per year with their GP (in-person, telephone, or E-mail consultation). General practice is characterized by 5 key components: (1) a list system, with an average of close to 1600 persons on the list of a typical GP; (2) the GP as gatekeeper and first-line provider in the sense that a referral from a GP is required for most office-based specialists and always for in- and outpatient hospital treatment; (3) an after-hours system staffed by GPs on a rota basis; (4) a mixed capitation and fee-for-service system; and (5) GPs are self-employed, working on contract for the public funder based on a national agreement that details not only services and reimbursement but also opening hours and required postgraduate education. The contract is (re)negotiated every 2 years. General practice is embedded in a universal tax-funded health care system in which GP and hospital services are free at the point of use. The current system has evolved over the past century and has shown an ability to adapt flexibly to new challenges. Practice units are fairly small: close to 2 GPs per unit plus nurses and secretaries. The units are fully computerized, that is, with computer-based patient records and submission of prescriptions digitally to pharmacies etc. Over the past few years a decrease in solo practices has been seen and is expected to accelerate, in part because of the GP age structure, with many GPs retiring and new GPs not wanting to practice alone. This latter workforce trend is pointing toward a new model with employed GPs, particularly in rural areas.
••
TL;DR: The model demonstrates that variation and selective retention of patterns of action are necessary and sufficient to explain the features of organizational routines that are most relevant in relation to dynamic capabilities, such as formation, inertia, endogenous change, and learning.
Abstract: This paper introduces a generative model of organizational routines and their change over time. The model demonstrates that variation and selective retention of patterns of action are necessary and sufficient to explain the features of organizational routines that are most relevant in relation to dynamic capabilities, such as formation, inertia, endogenous change, and learning. The model directly links micro-level actions to the macro-level dynamics of routines. The results suggest that focusing on action provides a useful and parsimonious foundation for a theory of organizational routines and capabilities.
••
TL;DR: New analytical technologies are revealing vanishingly low oxygen concentrations in nitrite-rich OMZs, indicating that these AMZs are essentially anoxic marine zones (AMZs), and previously unrecognized episodic intrusions of oxygen into the AMZ core are revealed, which could periodically support aerobic metabolisms in a typically anoxic environment.
Abstract: Vast expanses of oxygen-deficient and nitrite-rich water define the major oxygen minimum zones (OMZs) of the global ocean. They support diverse microbial communities that influence the nitrogen economy of the oceans, contributing to major losses of fixed nitrogen as dinitrogen (N2) and nitrous oxide (N2O) gases. Anaerobic microbial processes, including the two pathways of N2 production, denitrification and anaerobic ammonium oxidation, are oxygen-sensitive, with some occurring only under strictly anoxic conditions. The detection limit of the usual method (Winkler titrations) for measuring dissolved oxygen in seawater, however, is much too high to distinguish low oxygen conditions from true anoxia. However, new analytical technologies are revealing vanishingly low oxygen concentrations in nitrite-rich OMZs, indicating that these OMZs are essentially anoxic marine zones (AMZs). Autonomous monitoring platforms also reveal previously unrecognized episodic intrusions of oxygen into the AMZ core, which could periodically support aerobic metabolisms in a typically anoxic environment. Although nitrogen cycling is considered to dominate the microbial ecology and biogeochemistry of AMZs, recent environmental genomics and geochemical studies show the presence of other relevant processes, particularly those associated with the sulfur and carbon cycles. AMZs correspond to an intermediate state between two “end points” represented by fully oxic systems and fully sulfidic systems. Modern and ancient AMZs and sulfidic basins are chemically and functionally related. Global change is affecting the magnitude of biogeochemical fluxes and ocean chemical inventories, leading to shifts in AMZ chemistry and biology that are likely to continue well into the future.
••
Technische Universität München1, University of Mainz2, University of New South Wales3, University of Ulm4, University of Southern Denmark5, University of Texas MD Anderson Cancer Center6, University of Rostock7, University of Düsseldorf8, Tohoku University9, Korea University10, University of Florence11, University of Southern California12
TL;DR: Members of the Pancreatic Star Alliance discuss and consolidate current knowledge to outline and delineate areas of consensus or otherwise (eg, with regard to methodological approaches) and, more importantly, to identify essential directions for future research.
Abstract: The field of pancreatic stellate cell (PSC) biology is very young, as the essential in-vitro tools to study these cells (ie, methods to isolate and culture PSC) were only developed as recently as in 1998. Nonetheless, there has been an exponential increase in research output in this field over the past decade, with numerous research groups around the world focusing their energies into elucidating the biology and function of these cells. It is now well established that PSC are responsible for producing the stromal reaction (fibrosis) of two major diseases of the pancreas—chronic pancreatitis and pancreatic cancer. Despite exponentially increasing data, the methods for studying PSC remain variable. Although within individual laboratories methods are consistent, different methodologies used by various research groups make it difficult to compare results and conclusions. This article is not a review article on the functions of PSC. Instead, members of the Pancreatic Star Alliance (http://www.pancreaticstaralliance.com) discuss here and consolidate current knowledge, to outline and delineate areas of consensus or otherwise (eg, with regard to methodological approaches) and, more importantly, to identify essential directions for future research.
Hepatic stellate cells (HSC) were first described by Karl von Kupffer in 1876; however, similar cells in the pancreas were first observed in the 1980s.1–3 In 1998, Apte et al 4 and Bachem et al 5 isolated and cultured PSC.4 5 In the normal pancreas, PSC are located in close proximity to the basal aspect of pancreatic acinar cells. In sections immunostained for the marker desmin (a cytoskeletal protein), quiescent PSC can be seen as cells with a central cell body and long cytoplasmic projections extending along the base of adjacent acinar cells similar to that of pericytes in the mammary gland. …
••
University of Michigan1, Utrecht University2, Baylor College of Medicine3, University of California, San Diego4, Masaryk University5, Academy of Sciences of the Czech Republic6, Radboud University Nijmegen7, Genzyme8, University of Freiburg9, Newcastle University10, University of Cologne11, Harvard University12, Case Western Reserve University13, University of Texas Southwestern Medical Center14, University of Paris15, McGill University16, Istanbul University17, University of Strasbourg18, Indiana University19, University of Washington20, Duke University21, Hannover Medical School22, University of Münster23, University of California, Irvine24, St James's University Hospital25, Rockefeller University26, University of Southern Denmark27, Hebrew University of Jerusalem28, Howard Hughes Medical Institute29
TL;DR: It is shown that knockdown of CEP164 or ZNF423 causes sensitivity to DNA damaging agents and that cep164 knockdown in zebrafish results in dysregulated DDR and an NPHP-RC phenotype, and these findings link degenerative diseases of the kidney and retina, disorders of increasing prevalence, to mechanisms of DDR.
••
TL;DR: In this paper, an Interpretive Structured Modeling (ISM) was used for identifying and summarizing relationships among specific attributes for selecting the best third party reverse logistics provider among the ‘ n ’ 3PRLPs.