Showing papers by "University of Antwerp published in 2013"

Meta-analysis of 74,046 individuals identifies 11 new susceptibility loci for Alzheimer's disease

Abstract: Eleven susceptibility loci for late-onset Alzheimer's disease (LOAD) were identified by previous studies; however, a large portion of the genetic risk for this disease remains unexplained. We conducted a large, two-stage meta-analysis of genome-wide association studies (GWAS) in individuals of European ancestry. In stage 1, we used genotyped and imputed data (7,055,881 SNPs) to perform meta-analysis on 4 previously published GWAS data sets consisting of 17,008 Alzheimer's disease cases and 37,154 controls. In stage 2, 11,632 SNPs were genotyped and tested for association in an independent set of 8,572 Alzheimer's disease cases and 11,312 controls. In addition to the APOE locus (encoding apolipoprotein E), 19 loci reached genome-wide significance (P < 5 × 10−8) in the combined stage 1 and stage 2 analysis, of which 11 are newly associated with Alzheimer's disease.

Antibiotic resistance—the need for global solutions

Abstract: The causes of antibiotic resistance are complex and include human behaviour at many levels of society; the consequences affect everybody in the world. Similarities with climate change are evident. Many efforts have been made to describe the many different facets of antibiotic resistance and the interventions needed to meet the challenge. However, coordinated action is largely absent, especially at the political level, both nationally and internationally. Antibiotics paved the way for unprecedented medical and societal developments, and are today indispensible in all health systems. Achievements in modern medicine, such as major surgery, organ transplantation, treatment of preterm babies, and cancer chemotherapy, which we today take for granted, would not be possible without access to effective treatment for bacterial infections. Within just a few years, we might be faced with dire setbacks, medically, socially, and economically, unless real and unprecedented global coordinated actions are immediately taken. Here, we describe the global situation of antibiotic resistance, its major causes and consequences, and identify key areas in which action is urgently needed.

Hyperspectral Remote Sensing Data Analysis and Future Challenges

Abstract: Hyperspectral remote sensing technology has advanced significantly in the past two decades. Current sensors onboard airborne and spaceborne platforms cover large areas of the Earth surface with unprecedented spectral, spatial, and temporal resolutions. These characteristics enable a myriad of applications requiring fine identification of materials or estimation of physical parameters. Very often, these applications rely on sophisticated and complex data analysis methods. The sources of difficulties are, namely, the high dimensionality and size of the hyperspectral data, the spectral mixing (linear and nonlinear), and the degradation mechanisms associated to the measurement process such as noise and atmospheric effects. This paper presents a tutorial/overview cross section of some relevant hyperspectral data analysis methods and algorithms, organized in six main topics: data fusion, unmixing, classification, target detection, physical parameter retrieval, and fast computing. In all topics, we describe the state-of-the-art, provide illustrative examples, and point to future challenges and research directions.

Climate extremes and the carbon cycle

Abstract: The terrestrial biosphere is a key component of the global carbon cycle and its carbon balance is strongly influenced by climate. Continuing environmental changes are thought to increase global terrestrial carbon uptake. But evidence is mounting that climate extremes such as droughts or storms can lead to a decrease in regional ecosystem carbon stocks and therefore have the potential to negate an expected increase in terrestrial carbon uptake. Here we explore the mechanisms and impacts of climate extremes on the terrestrial carbon cycle, and propose a pathway to improve our understanding of present and future impacts of climate extremes on the terrestrial carbon budget.

Ecosystem-based coastal defence in the face of global change

Abstract: The risk of flood disasters is increasing for many coastal societies owing to global and regional changes in climate conditions, sea-level rise, land subsidence and sediment supply. At the same time, in many locations, conventional coastal engineering solutions such as sea walls are increasingly challenged by these changes and their maintenance may become unsustainable. We argue that flood protection by ecosystem creation and restoration can provide a more sustainable, cost-effective and ecologically sound alternative to conventional coastal engineering and that, in suitable locations, it should be implemented globally and on a large scale.

The C9orf72 GGGGCC Repeat Is Translated into Aggregating Dipeptide-Repeat Proteins in FTLD/ALS

Abstract: Expansion of a GGGGCC hexanucleotide repeat upstream of the C9orf72 coding region is the most common cause of familial frontotemporal lobar degeneration and amyotrophic lateral sclerosis (FTLD/ALS), but the pathomechanisms involved are unknown. As in other FTLD/ALS variants, characteristic intracellular inclusions of misfolded proteins define C9orf72 pathology, but the core proteins of the majority of inclusions are still unknown. Here, we found that most of these characteristic inclusions contain poly-(Gly-Ala) and, to a lesser extent, poly-(Gly-Pro) and poly-(Gly-Arg) dipeptide-repeat proteins presumably generated by non-ATG-initiated translation from the expanded GGGGCC repeat in three reading frames. These findings directly link the FTLD/ALS-associated genetic mutation to the predominant pathology in patients with C9orf72 hexanucleotide expansion.

Changing patterns in the epidemiology of traumatic brain injury

Abstract: Traumatic brain injury (TBI) is a critical public health and socio-economic problem throughout the world. Reliable quantification of the burden caused by TBI is difficult owing to inadequate standardization and incomplete capture of data on the incidence and outcome of brain injury, with variability in the definition of TBI being partly to blame. Reports show changes in epidemiological patterns of TBI: the median age of individuals who experience TBI is increasing, and falls have now surpassed road traffic incidents as the leading cause of this injury. Despite claims to the contrary, no clear decrease in TBI-related mortality or improvement of overall outcome has been observed over the past two decades. In this Perspectives article, we discuss the strengths and limitations of epidemiological studies, address the variability in its definition, and highlight changing epidemiological patterns. Taken together, these analyses identify a great need for standardized epidemiological monitoring in TBI.

Human-induced nitrogen–phosphorus imbalances alter natural and managed ecosystems across the globe

Abstract: Bioavailable nitrogen is increasing due to human activity, rapidly outpacing increases in another essential nutrient, phosphorous. Penuelas et al. show that this increasing imbalance between these nutrients is likely to significantly affect life and limit carbon storage in this century.

Anthropogenic perturbation of the carbon fluxes from land to ocean

Abstract: A substantial amount of the atmospheric carbon taken up on land through photosynthesis and chemical weathering is transported laterally along the aquatic continuum from upland terrestrial ecosystems to the ocean. So far, global carbon budget estimates have implicitly assumed that the transformation and lateral transport of carbon along this aquatic continuum has remained unchanged since pre-industrial times. A synthesis of published work reveals the magnitude of present-day lateral carbon fluxes from land to ocean, and the extent to which human activities have altered these fluxes. We show that anthropogenic perturbation may have increased the flux of carbon to inland waters by as much as 1.0 Pg C yr−1 since pre-industrial times, mainly owing to enhanced carbon export from soils. Most of this additional carbon input to upstream rivers is either emitted back to the atmosphere as carbon dioxide (~0.4 Pg C yr−1) or sequestered in sediments (~0.5 Pg C yr−1) along the continuum of freshwater bodies, estuaries and coastal waters, leaving only a perturbation carbon input of ~0.1 Pg C yr−1 to the open ocean. According to our analysis, terrestrial ecosystems store ~0.9 Pg C yr−1 at present, which is in agreement with results from forest inventories but significantly differs from the figure of 1.5 Pg C yr−1 previously estimated when ignoring changes in lateral carbon fluxes. We suggest that carbon fluxes along the land–ocean aquatic continuum need to be included in global carbon dioxide budgets.

Investigating the prevalence of complex fiber configurations in white matter tissue with diffusion magnetic resonance imaging.

Abstract: It has long been recognized that the diffusion tensor model is inappropriate to characterize complex fiber architecture, causing tensor-derived measures such as the primary eigenvector and fractional anisotropy to be unreliable or misleading in these regions. There is however still debate about the impact of this problem in practice. A recent study using a Bayesian automatic relevance detection (ARD) multicompartment model suggested that a third of white matter (WM) voxels contain crossing fibers, a value that, whilst already significant, is likely to be an underestimate. The aim of this study is to provide more robust estimates of the proportion of affected voxels, the number of fiber orientations within each WM voxel, and the impact on tensor-derived analyses, using large, high-quality diffusion-weighted data sets, with reconstruction parameters optimized specifically for this task. Two reconstruction algorithms were used: constrained spherical deconvolution (CSD), and the ARD method used in the previous study. We estimate the proportion of WM voxels containing crossing fibers to be ∼90% (using CSD) and 63% (using ARD). Both these values are much higher than previously reported, strongly suggesting that the diffusion tensor model is inadequate in the vast majority of WM regions. This has serious implications for downstream processing applications that depend on this model, particularly tractography, and the interpretation of anisotropy and radial/axial diffusivity measures.

Observation of a new boson with mass near 125 GeV in pp collisions at $ \sqrt{s}=7 $ and 8 TeV

Abstract: A detailed description is reported of the analysis used by the CMS Collaboration in the search for the standard model Higgs boson in pp collisions at the LHC, which led to the observation of a new boson. The data sample corresponds to integrated luminosities up to 5.1 inverse femtobarns at sqrt(s) = 7 TeV, and up to 5.3 inverse femtobarns at sqrt(s) = 8 TeV. The results for five Higgs boson decay modes gamma gamma, ZZ, WW, tau tau, and bb, which show a combined local significance of 5 standard deviations near 125 GeV, are reviewed. A fit to the invariant mass of the two high resolution channels, gamma gamma and ZZ to 4 ell, gives a mass estimate of 125.3 +/- 0.4 (stat) +/- 0.5 (syst) GeV. The measurements are interpreted in the context of the standard model Lagrangian for the scalar Higgs field interacting with fermions and vector bosons. The measured values of the corresponding couplings are compared to the standard model predictions. The hypothesis of custodial symmetry is tested through the measurement of the ratio of the couplings to the W and Z bosons. All the results are consistent, within their uncertainties, with the expectations for a standard model Higgs boson.

Diabetes Attitudes, Wishes and Needs second study (DAWN2™): Cross‐national benchmarking of diabetes‐related psychosocial outcomes for people with diabetes

Abstract: Aims The second Diabetes Attitudes, Wishes and Needs (DAWN2) study aimed to assess psychosocial outcomes in people with diabetes across countries for benchmarking. Methods Surveys included new and adapted questions from validated questionnaires that assess health-related quality of life, self-management, attitudes/beliefs, social support and priorities for improving diabetes care. Questionnaires were conducted online, by telephone or in person. Results Participants were 8596 adults with diabetes across 17 countries. There were significant between-country differences for all benchmarking indicators; no one country's outcomes were consistently better or worse than others. The proportion with likely depression [WHO-5 Well-Being Index (WHO-5) score ≤ 28] was 13.8% (country range 6.5–24.1%). Diabetes-related distress [Problem Areas in Diabetes Scale 5 (PAID-5) score ≥ 40] was reported by 44.6% of participants (17.2–67.6%). Overall quality of life was rated ‘poor’ or ‘very poor’ by 12.2% of participants (7.6–26.1%). Diabetes had a negative impact on all aspects investigated, ranging from 20.5% on relationship with family/friends to 62.2% on physical health. Approximately 40% of participants (18.6–64.9%) reported that their medication interfered with their ability to live a normal life. The availability of person-centred chronic illness care and support for active involvement was rated as low. Following self-care advice for medication and diet was most common, and least common for glucose monitoring and foot examination, with marked country variation. Only 48.8% of respondents had participated in diabetes educational programmes/activities to help manage their diabetes. Conclusions Cross-national benchmarking using psychometrically validated indicators can help identify areas for improvement and best practices to drive changes that improve outcomes for people with diabetes.

Plasma nanoscience: from nano-solids in plasmas to nano-plasmas in solids

Abstract: The unique plasma-specific features and physical phenomena in the organization of nanoscale soild-state systems in a broad range of elemental composition, structure, and dimensionality are critically reviewed. These effects lead to the possibility to localize and control energy and matter at nanoscales and to produce self-organized nano-solids with highly unusual and superior properties. A unifying conceptual framework based on the control of production, transport, and self-organization of precursor species is introduced and a variety of plasma-specific non-equilibrium and kinetics-driven phenomena across the many temporal and spatial scales is explained. When the plasma is localized to micrometer and nanometer dimensions, new emergent phenomena arise. The examples range from semiconducting quantum dots and nanowires, chirality control of single-walled carbon nanotubes, ultra-fine manipulation of graphenes, nano-diamond, and organic matter to nano-plasma effects and nano-plasmas of different states of matter.

Factors Affecting Auditory Performance of Postlinguistically Deaf Adults Using Cochlear Implants: An Update with 2251 Patients

Abstract: Objective: To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. Study Design: Retrospective multicenter study. Methods: Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. Results: The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. Conclusions: The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.

On the Validity of Student Evaluation of Teaching: The State of the Art

Abstract: This article provides an extensive overview of the recent literature on student evaluation of teaching (SET) in higher education. The review is based on the SET meta-validation model, drawing upon research reports published in peer-reviewed journals since 2000. Through the lens of validity, we consider both the more traditional research themes in the field of SET (i.e., the dimensionality debate, the ‘bias’ question, and questionnaire design) and some recent trends in SET research, such as online SET and bias investigations into additional teacher personal characteristics. The review provides a clear idea of the state of the art with regard to research on SET, thus allowing researchers to formulate suggestions for future research. It is argued that SET remains a current yet delicate topic in higher education, as well as in education research. Many stakeholders are not convinced of the usefulness and validity of SET for both formative and summative purposes. Research on SET has thus far failed to provide c...

Asymmetric effects of daytime and night-time warming on Northern Hemisphere vegetation

Abstract: Temperature data over the past five decades show faster warming of the global land surface during the night than during the day 1 . This asymmetric warming is expected to affect carbon assimilation and consumption in plants, because photosynthesis in most plants occurs during daytime and is more sensitive to the maximum daily temperature, Tmax, whereas plant respiration occurs throughout the day 2 and is therefore influenced by both Tmax and the minimum daily temperature, Tmin. Most studies of the response of terrestrial ecosystems to climate warming, however, ignore this asymmetric forcing effect on vegetation growth and carbon dioxide (CO2) fluxes 3–6 . Here we analyse the interannual covariations of the satellite-derived normalized difference vegetation index (NDVI, an indicator of vegetation greenness) with Tmax and Tmin over the Northern Hemisphere. After removing the correlation between Tmax and Tmin, we find that the partial correlation between Tmax and NDVI is positive in most wet and cool ecosystems over boreal regions, but negative in dry temperate regions. In contrast, the partial correlation between Tmin and NDVI is negative in boreal regions, and exhibits a more complex behaviour in dry temperate regions. We detect similar patterns in terrestrial net CO2 exchange maps obtained from a global atmospheric inversion model. Additional analysis of the long-term atmospheric CO2 concentration record of the station Point Barrow in Alaska suggests that the peak-to-peak amplitude of CO2 increased by 23 6 11% for a 11 6C anomaly in Tmax from May to September over lands north of 516 N, but decreased by 28 6 14% for a 11 6C anomaly in Tmin. These lines of evidence suggest that asymmetric diurnal warming, a process that is currently not taken into account in many global carbon cycle models, leads to a divergent response of Northern Hemisphere vegetation growth and carbon sequestration to rising temperatures. Both modelling and observational studies suggest that climate warming will probably enhance vegetation growth in northern terrestrial ecosystems, increasing carbon storage 3–6 . However, most of these studies do not consider the potential effects of asymmetric daytime and nighttime warming. The increasing rate of global land-surface daily minimum temperature (Tmin) over the past five decades is 1.4 times that of daily maximum temperature (Tmax) 1 . This asymmetric warming is expected to affect carbon assimilation and consumptions in plants, given that photosynthesis in most plants occurs during the daytime and thus is more sensitive to Tmax, whereas plant respiration occurs throughout the whole day 2 , and is therefore influenced by both Tmax

Plasma Nanoscience: from Nano-Solids in Plasmas to Nano-Plasmas in Solids

Abstract: The unique plasma-specific features and physical phenomena in the organization of nanoscale solid-state systems in a broad range of elemental composition, structure, and dimensionality are critically reviewed. These effects lead to the possibility to localize and control energy and matter at nanoscales and to produce self-organized nano-solids with highly unusual and superior properties. A unifying conceptual framework based on the control of production, transport, and self-organization of precursor species is introduced and a variety of plasma-specific non-equilibrium and kinetics-driven phenomena across the many temporal and spatial scales is explained. When the plasma is localized to micrometer and nanometer dimensions, new emergent phenomena arise. The examples range from semiconducting quantum dots and nanowires, chirality control of single-walled carbon nanotubes, ultra-fine manipulation of graphenes, nano-diamond, and organic matter, to nano-plasma effects and nano-plasmas of different states of matter.

Bidirectional transcripts of the expanded C9orf72 hexanucleotide repeat are translated into aggregating dipeptide repeat proteins

Abstract: Massive GGGGCC repeat expansion in the first intron of the gene C9orf72 is the most common known cause of familial frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Despite its intronic localization and lack of an ATG start codon, the repeat region is translated in all three reading frames into aggregating dipeptide-repeat (DPR) proteins, poly-(Gly-Ala), poly-(Gly-Pro) and poly-(Gly-Arg). We took an antibody-based approach to further validate the translation of DPR proteins. To test whether the antisense repeat RNA transcript is also translated, we raised antibodies against the predicted products, poly-(Ala-Pro) and poly-(Pro-Arg). Both antibodies stained p62-positive neuronal cytoplasmic inclusions throughout the cerebellum and hippocampus indicating that not only sense but also antisense strand repeats are translated into DPR proteins in the absence of ATG start codons. Protein products of both strands co-aggregate suggesting concurrent translation of both strands. Moreover, an antibody targeting the putative carboxyl terminus of DPR proteins can detect inclusion pathology in C9orf72 repeat expansion carriers suggesting that the non-ATG translation continues through the entire repeat and beyond. A highly sensitive monoclonal antibody against poly-(Gly-Arg), visualized abundant inclusion pathology in all cortical regions and some inclusions also in motoneurons. Together, our data show that the GGGGCC repeat is bidirectionally translated into five distinct DPR proteins that co-aggregate in the characteristic p62-positive TDP-43 negative inclusions found in FTLD/ALS cases with C9orf72 repeat expansion. Novel monoclonal antibodies against poly-(Gly-Arg) will facilitate pathological diagnosis of C9orf72 FTLD/ALS.

Anomalous Raman spectra and thickness-dependent electronic properties of WSe2

Abstract: Typical Raman spectra of transition metal dichalcogenides (TMDs) display two prominent peaks, E2g and A1g, that are well separated from each other. We find that these modes are degenerate in bulk WSe2 yielding one single Raman peak. As the dimensionality is lowered, the observed peak splits in two as a result of broken degeneracy. In contrast to our experimental findings, our phonon dispersion calculations reveal that these modes remain degenerate independent of the number of layers. Interestingly, for minuscule biaxial strain the degeneracy is preserved but once the crystal symmetry is broken by uniaxial strain, the degeneracy is lifted. Our calculated phonon dispersion for uniaxially strained WSe2 shows a perfect match to the measured Raman spectrum which suggests that uniaxial strain exists in WSe2 flakes possibly induced during the sample preparation and/or as a result of interaction between WSe2 and the substrate. Furthermore, we find that WSe2 undergoes an indirect to direct bandgap transition from bulk to monolayers which is ubiquitous for semiconducting TMDs. These results not only allow us to understand the vibrational properties of WSe2 but also provides detailed insight to their physical properties.

Prophylactic vaccination against human papillomaviruses to prevent cervical cancer and its precursors

Abstract: Background Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide. Objectives To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women. Search methods We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events. Selection criteria Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine). Data collection and analysis We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2(+)], CIN grade 3 and above [CIN3(+)], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets. Main results We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation. Efficacy endpoints by initial HPV DNA statushr HPV negative HPV vaccines reduce CIN2(+), CIN3(+), AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2(+) from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3(+) from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82). HPV vaccines reduce the risk of any CIN2(+) from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3(+) with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison. HPV16/18 negative In those aged 15 to 26 years, vaccines reduce CIN2(+) associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3(+) and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes. Vaccines reduce any CIN2(+) from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions. Regardless of HPV DNA status In younger women HPV vaccines reduce the risk of CIN2(+) associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3(+) associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty). HPV vaccines reduce any CIN2(+) from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3(+) differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)). In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2(+) associated with HPV16/18 and any CIN2(+) are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3(+) or AIS. Adverse effects The risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established. Pregnancy outcomes Among those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively). Authors' conclusions There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2(+) in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status. We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.

Life cycle assessment in the construction sector: A review

Abstract: The last decades, lowering the ecological impact of buildings is receiving increased attention by researchers, policy-makers and companies. Mostly the focus is on reducing energy consumption and the use of eco-friendly materials, but the concept of life-cycle thinking is growing in importance. This paper tries to give an overview of the current situation of Life cycle assessment (LCA) in the construction industry, both of regulatory developments and academic case studies. After a short history of LCA, the focus is on LCA methodology, new standards and frameworks and an extensive selection of recent case studies. Despite some inherent limitations of LCA as an analytic tool and fundamental differences between the individual cases, still some common trends can be indicated. In standard buildings, the use phase contributes up to 90% of the total environmental burdens, mainly due to heating and/or cooling. Due to regulations, new buildings become more energy efficient, and thereby other phases of the life cycle gain in importance e.g., choice of materials, construction, end-of-life and water use. These research topics deserve more attention, together with economic issues, the improvement of data quality and implementation of probability density distributions.

Antimicrobial resistance: a global view from the 2013 World Healthcare-Associated Infections Forum

Abstract: Antimicrobial resistance (AMR) is now a global threat. Its emergence rests on antimicrobial overuse in humans and food-producing animals; globalization and suboptimal infection control facilitate its spread. While aggressive measures in some countries have led to the containment of some resistant gram-positive organisms, extensively resistant gram-negative organisms such as carbapenem-resistant enterobacteriaceae and pan-resistant Acinetobacter spp. continue their rapid spread. Antimicrobial conservation/stewardship programs have seen some measure of success in reducing antimicrobial overuse in humans, but their reach is limited to acute-care settings in high-income countries. Outside the European Union, there is scant or no oversight of antimicrobial administration to food-producing animals, while evidence mounts that this administration leads directly to resistant human infections. Both horizontal and vertical infection control measures can interrupt transmission among humans, but many of these are costly and essentially limited to high-income countries as well. Novel antimicrobials are urgently needed; in recent decades pharmaceutical companies have largely abandoned antimicrobial discovery and development given their high costs and low yield. Against this backdrop, international and cross-disciplinary collaboration appears to be taking root in earnest, although specific strategies still need defining. Educational programs targeting both antimicrobial prescribers and consumers must be further developed and supported. The general public must continue to be made aware of the current scale of AMR’s threat, and must perceive antimicrobials as they are: a non-renewable and endangered resource.

A Multicenter Study of Glucocerebrosidase Mutations in Dementia With Lewy Bodies

Abstract: IMPORTANCE: While mutations in glucocerebrosidase (GBA1) are associated with an increased risk for Parkinson disease (PD), it is important to establish whether such mutations are also a common risk factor for other Lewy body disorders. OBJECTIVE: To establish whether GBA1 mutations are a risk factor for dementia with Lewy bodies (DLB). DESIGN We compared genotype data on patients and controls from 11 centers. Data concerning demographics, age at onset, disease duration, and clinical and pathological features were collected when available. We conducted pooled analyses using logistic regression to investigate GBA1 mutation carrier status as predicting DLB or PD with dementia status, using common control subjects as a reference group. Random-effects meta-analyses were conducted to account for additional heterogeneity. SETTING: Eleven centers from sites around the world performing genotyping. PARTICIPANTS: Seven hundred twenty-one cases met diagnostic criteria for DLB and 151 had PD with dementia. We compared these cases with 1962 controls from the same centers matched for age, sex, and ethnicity. MAIN OUTCOME MEASURES: Frequency of GBA1 mutations in cases and controls. RESULTS We found a significant association between GBA1 mutation carrier status and DLB, with an odds ratio of 8.28 (95% CI, 4.78-14.88). The odds ratio for PD with dementia was 6.48 (95% CI, 2.53-15.37). The mean age at diagnosis of DLB was earlier in GBA1 mutation carriers than in noncarriers (63.5 vs 68.9 years; P < .001), with higher disease severity scores. CONCLUSIONS AND RELEVANCE: Mutations in GBA1 are a significant risk factor for DLB. GBA1 mutations likely play an even larger role in the genetic etiology of DLB than in PD, providing insight into the role of glucocerebrosidase in Lewy body disease.