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Background: Patients with dementia have an increased risk of developing epilepsy, especially in patients with vascular dementia and Alzheimer’s disease. In selecting the optimal anti- epileptic drug (AED), the possible side effects such as drowsiness and worsening of cognitive function should be taken into consideration, together with co-morbidities and type of epilepsy. Objective: The current systematic review investigates the efficacy, tolerability, and changes in cognitive function after administration of AED in patients with dementia and epilepsy. Methods: We searched six databases, including MEDLINE and CENTRAL, checked reference lists, contacted experts, and searched Google Scholar to identify studies reporting randomized trials. Studies identified were independently screened, data extracted, and quality appraised by two researchers. A narrative synthesis was used to report findings. Results: We included one study with 95 patients with Alzheimer’s disease randomized to either levetiracetam, lamotrigine, or phenobarbital. No significant differences were found for efficacy, but patients receiving levetiracetam showed an improvement in mini-mental state examination scores and had fewer adverse events. Conclusion: High-quality evidence in the form of randomized controlled trials to guide clinicians in choosing an AED in patients with dementia and concomitant epilepsy remains scarce. However, levetiracetam has previously been shown to possibly improve cognition in patients with both mild cognitive impairment and Alzheimer’s disease, is better tolerated in the elderly population, and has no clinically relevant interaction with either cholinesterase inhibitors or NMDA receptor antagonists.

The G4C2-repeat expansion in C9orf72 is the most common cause of frontotemporal dementia and of amyotrophic lateral sclerosis. The variability of age at onset and phenotypic presentations is a hallmark of C9orf72 disease. In this study, we aimed to identify modifying factors of disease onset in C9orf72 carriers using a family-based approach, in pairs of C9orf72 carrier relatives with concordant or discordant age at onset. Linkage and association analyses provided converging evidence for a locus on chromosome Xq27.3. The minor allele A of rs1009776 was associated with an earlier onset (P = 1 × 10−5). The association with onset of dementia was replicated in an independent cohort of unrelated C9orf72 patients (P = 0.009). The protective major allele delayed the onset of dementia from 5 to 13 years on average depending on the cohort considered. The same trend was observed in an independent cohort of C9orf72 patients with extreme deviation of the age at onset (P = 0.055). No association of rs1009776 was detected in GRN patients, suggesting that the effect of rs1009776 was restricted to the onset of dementia due to C9orf72. The minor allele A is associated with a higher SLITRK2 expression based on both expression quantitative trait loci (eQTL) databases and in-house expression studies performed on C9orf72 brain tissues. SLITRK2 encodes for a post-synaptic adhesion protein. We further show that synaptic vesicle glycoprotein 2 and synaptophysin, two synaptic vesicle proteins, were decreased in frontal cortex of C9orf72 patients carrying the minor allele. Upregulation of SLITRK2 might be associated with synaptic dysfunctions and drives adverse effects in C9orf72 patients that could be modulated in those carrying the protective allele. How the modulation of SLITRK2 expression affects synaptic functions and influences the disease onset of dementia in C9orf72 carriers will require further investigations. In summary, this study describes an original approach to detect modifier genes in rare diseases and reinforces rising links between C9orf72 and synaptic dysfunctions that might directly influence the occurrence of first symptoms.

BACKGROUND: The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level "suggestive of progressive supranuclear palsy" for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. OBJECTIVE: To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy-confirmed cohort. METHODS: Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy-confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. RESULTS: The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two-thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. CONCLUSIONS: Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real-life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Secondary AML (s-AML), including AML with an antecedent hematologic disorder (AHD-AML) and therapy-related AML (t-AML), constitutes a large proportion of patients with AML and is considered to confer a dismal prognosis. The role of allogeneic hematopoietic cell transplantation (HCT) in patients with s-AML and the extent to which HCT is performed in these patients has been little studied to date. We used the population-based Swedish AML Registry comprising 3337 intensively treated adult patients over a 17-year period to study the role of HCT within the group of patients with s-AML as well as compared with patients with de novo AML. HCT was performed in 576 patients (22%) with de novo AML, in 74 patients (17%) with AHD-AML, and in 57 patients (20%) with t-AML. At 5 years after diagnosis, there were no survivors among patients with previous myeloproliferative neoplasms who did not undergo HCT, and corresponding survival for patients with antecedent myelodysplastic syndromes and t-AML was and 2% and 4%, respectively. HCT was compared with chemotherapy consolidation in s-AML using 3 models: (1) a 200-day landmark analysis, in which HCT was favorable compared with conventional consolidation (P = .04, log-rank test); (2) a multivariable Cox regression with HCT as a time-dependent variable, in which the hazard ratio for mortality was 0.73 (95% confidence interval, 0.64 to 0.83) for HCT and favored HCT in all subgroups; and (3) a propensity score matching analysis, in which the 5-year overall survival (OS) and relapse-free survival in patients with s-AML in first complete remission (CR1) was 48% and 43%, respectively, for patients undergoing HCT versus 20% and 21%, respectively, for those receiving chemotherapy consolidation (P = .01 and .02, respectively, log-rank test). Our observational data suggest that HCT improves survival and offers the only realistic curative treatment option in patients with s-AML.

BACKGROUND: Dementia is a syndrome, with a wide range of symptoms. It is important to have a timely diagnosis during the disease course to reduce the risk of medication errors, enable future care planning for the patient and their relatives thereby optimizing quality of life (QoL). For this reason, it is important to avoid a diagnosis of dementia not otherwise specified (DNOS) and instead obtain a diagnosis that reflects the underlying pathology. The aim of this study was to investigate the prevalence and associated factors of DNOS in persons with dementia living at home or in a nursing home. METHODS: This is a cross-sectional cohort study performed in eight European countries. Persons with dementia aged ≥65 years living at home (n = 1223) or in a nursing home (n = 790) were included. Data were collected through personal interviews with questionnaires based on standardised instruments. Specific factors investigated were sociodemographic factors, cognitive function, and mental health, physical health, QoL, resource utilization and medication. Bivariate and backward stepwise multivariate regression analyses were performed. RESULTS: The prevalence of DNOS in the eight participating European countries was 16% (range 1-30%) in persons living at home and 21% (range 1-43%) in persons living in a nursing home. These people are more often older compared to those with a specific dementia diagnosis. In both persons living at home and persons living in a nursing home, DNOS was associated with more severe neuropsychiatric symptoms and less use of anti-dementia medication. In addition, persons with DNOS living at home had more symptoms of depression and less use of antidepressant medication. CONCLUSIONS: The prevalence of DNOS diagnosis is common and seems to vary between European countries. People with DNOS are more often older with more severe neuropsychiatric symptoms and receive fewer anti-dementia medication, anxiolytics and antidepressants. This would support the suggestion that a proper and specific diagnosis of dementia could help the management of their disease. This study was supported by grants from the Greta and Johan Kocks Foundation and Skåne University Hospitals Foundations in Sweden. The RTPC study was supported by a grant from the European Commission within the 7th Framework Programme (contract number 242153).

Objective: Diagnosis of frontotemporal dementia (FTD) is complicated by the overlap of clinical symptoms with other dementia disorders. Development of robust fluid biomarkers is critical to improve the diagnostic work-up of FTD. Methods: CSF concentrations of placental growth factor (PlGF) were measured in the discovery cohort including patients with FTD (n = 27), Alzheimer disease (AD) dementia (n = 75), DLB or PDD (n = 47), subcortical vascular dementia (VaD, n = 33), mild cognitive impairment that later converted to AD (MCI-AD, n = 34), stable MCI (sMCI, n = 62), and 50 cognitively healthy controls from the Swedish BioFINDER study. For validation, CSF PlGF was measured in additional independent cohort of FTD patients (n = 22) and controls (n = 18) from the Netherlands. Results: In the discovery cohort, MCI, MCI-AD, AD dementia, DLB-PDD, VaD, and FTD patients all showed increased CSF levels of PlGF compared with controls (sMCI P = 0.019; MCI-AD P = 0.005; AD dementia, DLB-PDD, VaD, and FTD all P

BACKGROUND: The Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them. METHODS: We retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations. RESULTS: Comprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1. CONCLUSIONS: The proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society.

Describe PSP Study Group, the ProPSP Study Group, and the Movement Disorder Society–Endorsed PSP Study Group., [Background] The Progressive Supranuclear Palsy Rating Scale is a prospectively validated physician-rated measure of disease severity for progressive supranuclear palsy. We hypothesized that, according to experts' opinion, individual scores of items would differ in relevance for patients' quality of life, functionality in daily living, and mortality. Thus, changes in the score may not equate to clinically meaningful changes in the patient's status., [Objective] The aim of this work was to establish a condensed modified version of the scale focusing on meaningful disease milestones., [Methods] Sixteen movement disorders experts evaluated each scale item for its capacity to capture disease milestones (0 = no, 1 = moderate, 2 = severe milestone). Items not capturing severe milestones were eliminated. Remaining items were recalibrated in proportion to milestone severity by collapsing across response categories that yielded identical milestone severity grades. Items with low sensitivity to change were eliminated, based on power calculations using longitudinal 12-month follow-up data from 86 patients with possible or probable progressive supranuclear palsy., [Results] The modified scale retained 14 items (yielding 0–2 points each). The items were rated as functionally relevant to disease milestones with comparable severity. The modified scale was sensitive to change over 6 and 12 months and of similar power for clinical trials of disease-modifying therapy as the original scale (achieving 80% power for two-sample t test to detect a 50% slowing with n = 41 and 25% slowing with n = 159 at 12 months)., [Conclusions] The modified Progressive Supranuclear Palsy Rating Scale may serve as a clinimetrically sound scale to monitor disease progression in clinical trials and routine. © 2021 International Parkinson and Movement Disorder Society., This work was supported by the Munich Cluster for Systems Neurology (Synergy), the Volkswagen Stiftung, the Lower Saxony Ministry for Science, the Niedersächsisches Vorab, and the Petermax-Müller Foundation (Etiology and Therapy of Synucleinopathies and Tauopathies). This project was also supported by the German Center for Neurodegenerative Diseases e.V. (DZNE), German PSP Gesellschaft, and the International Parkinson & Movement Disorder Society.

Non-technical summary There has been a long history of conflicts, studies, and debate over how to both protect rivers and develop them sustainably. With a pause in new developments caused by the global pandemic, anticipated further implementation of the Paris Agreement and high-level global climate and biodiversity meetings in 2021, now is an opportune moment to consider the current trajectory of development and policy options for reconciling dams with freshwater system health. Technical summary We calculate potential loss of free-flowing rivers (FFRs) if proposed hydropower projects are built globally. Over 260,000 km of rivers, including Amazon, Congo, Irrawaddy, and Salween mainstem rivers, would lose free-flowing status if all dams were built. We propose a set of tested and proven solutions to navigate trade-offs associated with river conservation and dam development. These solution pathways are framed within the mitigation hierarchy and include (1) avoidance through either formal river protection or through exploration of alternative development options; (2) minimization of impacts through strategic or system-scale planning or re-regulation of downstream flows; (3) restoration of rivers through dam removal; and (4) mitigation of dam impacts through biodiversity offsets that include restoration and protection of FFRs. A series of examples illustrate how avoiding or reducing impacts on rivers is possible – particularly when implemented at a system scale – and can be achieved while maintaining or expanding benefits for climate resilience, water, food, and energy security. Social media summary Policy solutions and development pathways exist to navigate trade-offs to meet climate resilience, water, food, and energy security goals while safeguarding FFRs.

Mechanisms for late-onset neutropenia (LON) after rituximab treatment are poorly defined both for non-Hodgkin lymphoma (NHL) and for autoimmune disorders. We performed a case–control analysis of a prospective cohort of 169 evaluable consecutive rituximab-treated NHL patients to assess cytokines involved in neutro- and lymphopoiesis (G-CSF, SDF1, BAFF, APRIL) and inflammation (CRP) as possible LON mechanisms. Fifteen patients (9%) developed LON (peripheral blood /PB/ absolute neutrophil counts /ANC/

Funder: QingLan Research Project of Jiangsu for Outstanding Young Teachers, Funder: Project funded by Postdoctoral Science Foundation of Xuzhou Medical University, Funder: Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical University, We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.

Longitudinal studies of caregiver burden when caring for persons with dementia living at home are sparse. The aim of the study was to identify factors associated with caregiver burden and predicting increased burden related to caregivers, persons with dementia and formal care. Data were collected through interviews with 1223 caregivers in eight European countries. Bivariate and multivariate regression analyses were performed. Factors associated with caregiver burden included extensive informal care provision, decreased well-being and reduced quality of life for the caregiver and reduced cognition, decreased quality of life, severe neuropsychiatric symptoms and depression in the person with dementia and caregivers’ negative experience of quality of care. Factors predicting an increased burden were diminished caregiver well-being, severe neuropsychiatric symptoms of the person with dementia and caregivers’ negative perception of quality of care. The knowledge gained in this study may be useful in developing more adequate service systems and interventions to improve dementia care.

Relevant molecular tools for treatment stratification of patients ≥65 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA- and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients ≥65 years. Intensively treated patients with NPM1 and IDH2R172 mutations had longer overall survival (OS), whereas mutated TP53 conferred lower CR rates and shorter OS. FLT3-ITD and TP53 mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutated TP53, compared to 97% CR in low-risk patients defined by high expression of ZBTB7A and EEPD1 without TP53 mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.

Hydropeaking, defined as frequent and rapid variation in flow in regulated rivers with hydropower plants over a short period of time, usually sub-daily to weekly, alters hydraulic parameters such as water levels or flow velocity and exerts strong impacts on fluvial ecosystems. We evaluated the effects of hydropeaking on riverbank vegetation, specifically assessing the germination and establishment of seedlings and cuttings of plant species representing a variation in traits. We used seeds and seedlings and cuttings varying in size as phytometers, and transplanted them to riverbanks both above and below dams used for hydropower production in northern Sweden, selected to represent a gradient in hydropeaking intensity, and along a free-flowing reach. We also analyzed sub-daily water-level variables modified by hydropeaking to identify variables key in explaining the observed vegetation patterns. We found that plant responses to hydropeaking varied with species, with flood-intolerant species being the most strongly affected, as early as the germination stage. In contrast, seeds of flood-tolerant species managed to germinate and survive the early establishment phase, although strong erosive processes triggered by hydropeaking eventually caused most of them to fail. The fate of flood-intolerant species identifies germination as the most critical life-history stage. The depth and frequency of the inundation were the leading variables explaining plant responses, while the duration of shallow inundation explained little of the variation. The rise and fall rates of water levels were key in explaining variation in germination success. Based on the results, we propose restoration measures to enhance establishment of riparian plant communities while minimizing the impact on hydropower electricity production. Given the strong decrease in the germination of species intolerant to prolonged flooding with hydropeaking, planting of seedlings, preferably of large sizes, together with restrictions in the operation of the power plant during the establishment phase to enhance survival would be the best restoration option. Given the high probability of plant uprooting with hydropeaking, bank protection measures have the potential to increase riparian plant survival of all species, including flooding-tolerant species.

1. Many riparian ecosystems in Mediterranean Europe are affected by land use and flow alteration by dams. We focused on understanding how these stressors and their components affect riparian forest ...

Background-Aim: Infection from SARS-CoV-2 has emerged as new pathological entity within the global medical community. One of the earliest questions was in relation to the ability of the immunocompromised patients to clear the infection. In COST EuNet-INNOCHRON we were interested in the impact of SARS-CoV-2 infection in patients with different types of chronic neutropenia (CNP). The aim of the current study is to understand the impact of SARS-CoV-2 infection and to identify any possible characteristic patterns of the clinical course in patients with CNP. Patients and Methods: The COST EuNet-INNOCHRON Action in collaboration with the European Haematology Association - Scientific Working Group (EHA-SWG) on Granulocytes and Constitutional Marrow Failure Syndromes has conducted an online survey on SARS-CoV-2 infection in patients with CNP. The EuNet-INNOCHRON participants from different countries got access to an on-line platform fulfilling the General Data Protection Regulation (GDPR) and could register adult and paediatric CNP patients who had been infected by SARS-CoV-2 from March 2020 to June 2021. Data on demographic characteristics, type of CNP, patients' background and SARS-CoV-2 infection history (symptoms, laboratory features, radiological appearance, therapeutic approach and outcome) were collected. Results: Twenty-six patients with diagnosis of CNP, 7 males and 19 females were registered. Patient age distribution as follows: 16 patients >18 years old (y.o.)5 patients 5-18 y.o, 4 patients < 5 y.o whereas age was not available for one of the patients. Nine of the patients were diagnosed with idiopathic CNP, 7 patients with congenital neutropenia (6 of them with severe congenital neutropenia), 3 with secondary CNP, 2 with suspected autoimmune neutropenia of infancy (although antineutrophil Ab were negative), one with autoimmune neutropenia, one with drug induced neutropenia and 3 with other types of CNP. Twelve patients were on treatment with G-CSF and 6 patients had a history of previous viral or bacterial infections. Clonal Cytopenia(s) of Undetermined Significance (CCUS) was excluded in the eight patients who were investigated. Twenty-four out of 26 patients had positive PCR and one was found incidentally with positive antibodies for SARS-CoV-2. One more patient was symptomatic with history of close contact with SARS-CoV-2 infected family members. The commonest observed symptoms were fever >38 oC (19 patients), cough (10 patients), rhinorrhoea (10 patients), sore throat (6 patients), musculoskeletal pains (7 patients), taste/smell loss (5 patients), headache (5 patients), dyspnoea (4 patients), chest pain (one patient) and none of them had gastrointestinal symptoms. No other associated respiratory viral or bacterial infections were reported. Four patients who had one or more underlying conditions (immune deficiency, heart/respiratory/kidney disease) were admitted in hospital and needed anti SARS-CoV-2 treatment. Two of them had non-invasive ventilation and one of them needed admission in intensive care unit (ICU); both recovered. Another patient with Fallot's tetralogy needed mechanical ventilation in ICU and sadly passed away. No other deaths were observed. Deterioration of the pre-existing neutropenia was seen in two patients, two patients developed thrombocytopenia, one patient developed worsening lymphopenia and one anaemia. Twelve patients had chest X-ray and consolidation was found in two of them. All three patients who had chest CT scans were found with ground-glass changes. During the observation period (up to two months), no re-infection from SARS-CoV-2 was found. The Stockholm, Sweden experience is similar to the above data. One hundred fifty-four patients with CNP were followed up, for 10 months (March 1 to December 31, 2020) for SARS-CoV-2. Seventeen of these (i.e. 11 %) were infected. None needed hospitalization and there were no fatalities. Conclusion: Although the relative susceptibility of neutropenic patients to contract SARS-CoV-2 needs to be assessed with further studies, the clinical course and severity of SARS-CoV-2 infection doesn't seem to be worse in CNP patients (regardless the type of neutropenia and the need for GCSF treatment) compared to the general population. Also, like what has been observed in non-neutropenic patients, underlying comorbidities is a significant risk factor for severe disease and adverse outcome. Disclosures Dale: X4 Pharmaceuticals: Consultancy, Honoraria, Research Funding. Palmblad: Chiesi Ltd Sweden: Honoraria; Roche Sweden: Speakers Bureau; Chiesi Ltd Candada,: Honoraria.

Summary Background Most patients with Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies do not carry mutations in known disease-causing genes. The aim of this study was to identify a novel gene implicated in the development of these disorders. Methods Our study was done in three stages. First, we did genome-wide linkage analysis of an Italian family with dominantly inherited Parkinson's disease to identify the disease locus. Second, we sequenced the candidate gene in an international multicentre series of unrelated probands who were diagnosed either clinically or pathologically with Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies. As a control, we used gene sequencing data from individuals with abdominal aortic aneurysms (who were not examined neurologically). Third, we enrolled an independent series of patients diagnosed clinically with Parkinson's disease and controls with no signs or family history of Parkinson's disease, Parkinson's disease dementia, or dementia with Lewy bodies from centres in Portugal, Sardinia, and Taiwan, and screened them for specific variants. We also did mRNA and brain pathology studies in three patients from the international multicentre series carrying disease-associated variants, and we did functional protein studies in in-vitro models, including neurons from induced pluripotent stem-like cells. Findings Molecular studies were done between Jan 1, 2008, and Dec 31, 2017. In the initial kindred of ten affected Italian individuals (mean age of disease onset 59·8 years [SD 8·7]), we detected significant linkage of Parkinson's disease to chromosome 14 and nominated LRP10 as the disease-causing gene. Among the international series of 660 probands, we identified eight individuals (four with Parkinson's disease, two with Parkinson's disease dementia, and two with dementia with Lewy bodies) who carried different, rare, potentially pathogenic LRP10 variants; one carrier was found among 645 controls with abdominal aortic aneurysms. In the independent series, two of these eight variants were detected in three additional Parkinson's disease probands (two from Sardinia and one from Taiwan) but in none of the controls. Of the 11 probands from the international and independent cohorts with LRP10 variants, ten had a positive family history of disease and DNA was available from ten affected relatives (in seven of these families). The LRP10 variants were present in nine of these ten relatives, providing independent—albeit limited—evidence of co-segregation with disease. Post-mortem studies in three patients carrying distinct LRP10 variants showed severe Lewy body pathology. Of nine variants identified in total (one in the initial family and eight in stage 2), three severely affected LRP10 expression and mRNA stability (1424+5delG, 1424+5G→A, and Ala212Serfs*17, shown by cDNA analysis), four affected protein stability (Tyr307Asn, Gly603Arg, Arg235Cys, and Pro699Ser, shown by cycloheximide-chase experiments), and two affected protein localisation (Asn517del and Arg533Leu; shown by immunocytochemistry), pointing to loss of LRP10 function as a common pathogenic mechanism. Interpretation Our findings implicate LRP10 gene defects in the development of inherited forms of α-synucleinopathies. Future elucidation of the function of the LRP10 protein and pathways could offer novel insights into mechanisms, biomarkers, and therapeutic targets. Funding Stichting ParkinsonFonds, Dorpmans-Wigmans Stichting, Erasmus Medical Center, ZonMw—Memorabel programme, EU Joint Programme Neurodegenerative Disease Research (JPND), Parkinson's UK, Avtal om Lakarutbildning och Forskning (ALF) and Parkinsonfonden (Sweden), Lijf and Leven foundation, and cross-border grant of Alzheimer Netherlands–Ligue Europeene Contre la Maladie d'Alzheimer (LECMA).

Hydropeaking refers to frequent, rapid and short-term fluctuations in water flow and water levels downstream and upstream of hydropower stations. Such fluctuations are becoming increasingly common worldwide and are known to have far-reaching effects on riverine vegetation. Novel hydrology caused by hydropeaking has no natural correspondence in freshwater systems, and hence few species have adaptations to all its aspects. Here, we review the literature on hydropeaking effects on riverine plants and define the state of the information on this human alteration of riverine ecosystems. We focus on riparian plants, but also draw on information from aquatic plant species, which exhibit a wide variety of adaptations to inundation and associated processes. Riparian plants face both physiological and physical constraints because of the shifts between submergence and drainage, and erosion of substrates. At the population level, hydropeaking may favour dispersal within, but not between, reservoirs, but may hamper germination, establishment, growth and reproduction. At the community level, strong filtering towards easily dispersed, flexible, flood-tolerant and amphibious plants is expected, although few species share these traits. Hence, most riparian plant species are expected to disappear or be pushed towards the upper boundaries of the regulated river margin. Future research should examine more closely global variation in hydropeaking effects, including other taxonomic groups of species and the diversity of hydropeaking regimes. There is also a need for studies focusing on identifying the boundaries within which hydropeaking could operate without impairing plant life.

Riparian zones are the interface between aquatic and terrestrial systems along inland watercourses. They have a disproportionate ecological role in the landscape considering their narrow extent, wh ...

A characterization of short-term changes in river flow is essential for understanding the ecological effects of hydropower plants, which operate by turning the turbines on or off to generate electricity following variations in the market demand (i.e., hydropeaking). The goal of our study was to develop an approach for characterizing the effects of hydropower plant operations on within-day flow regimes across multiple dams and rivers. For this aim we first defined ecologically meaningful metrics that provide a full representation of the flow regime at short time scales from free-flowing rivers and rivers exposed to hydropeaking. We then defined metrics that enable quantification of the deviation of the altered short-term flow regime variables from those of the unaltered state. The approach was successfully tested in two rivers in northern Sweden, one free-flowing and another regulated by cascades of hydropower plants, which were additionally classified based on their impact on short-term flows in sites of similar management. The largest differences between study sites corresponded to metrics describing sub-daily flow magnitudes such as amplitude (i.e., difference between the highest and the lowest hourly flows) and rates (i.e., rise and fall rates of hourly flows). They were closely followed by frequency-related metrics accounting for the numbers of within-day hourly flow patterns (i.e., rises, falls and periods of stability of hourly flows). In comparison, between-site differences for the duration-related metrics were smallest. In general, hydropeaking resulted in higher within-day flow amplitudes and rates and more but shorter periods of a similar hourly flow patterns per day. The impacted flow feature and the characteristics of the impact (i.e., intensity and whether the impact increases or decreases whatever is being described by the metric) varied with season. Our approach is useful for catchment management planning, defining environmental flow targets, prioritizing river restoration or dam reoperation efforts and contributing information for relicensing hydropower dams.

Risk stratification of acute myeloid leukemia (AML) patients needs improvement. Several AML risk classification models based on somatic mutations or gene-expression profiling have been proposed. However, systematic and independent validation of these models is required for future clinical implementation. We performed whole-transcriptome RNA-sequencing and panel-based deep DNA sequencing of 23 genes in 274 intensively treated AML patients (Clinseq-AML). We also utilized the The Cancer Genome Atlas (TCGA)-AML study (N=142) as a second validation cohort. We evaluated six previously proposed molecular-based models for AML risk stratification and two revised risk classification systems combining molecular- and clinical data. Risk groups stratified by five out of six models showed different overall survival in cytogenetic normal-AML patients in the Clinseq-AML cohort (P-value0.5). Risk classification systems integrating mutational or gene-expression data were found to add prognostic value to the current European Leukemia Net (ELN) risk classification. The prognostic value varied between models and across cohorts, highlighting the importance of independent validation to establish evidence of efficacy and general applicability. All but one model replicated in the Clinseq-AML cohort, indicating the potential for molecular-based AML risk models. Risk classification based on a combination of molecular and clinical data holds promise for improved AML patient stratification in the future.

Neurofilaments are structural components of neurons and are particularly abundant in highly myelinated axons. The levels of neurofilament light chain (NfL) in both cerebrospinal fluid (CSF) and plasma have been related to degeneration in several neurodegenerative conditions including frontotemporal dementia (FTD) and NfL is currently considered as the most promising diagnostic and prognostic fluid biomarker in FTD. Although the location and function of filaments in the healthy nervous system suggests a link between increased NfL and white matter degeneration, such a claim has not been fully elucidated in vivo , especially in the context of FTD. The present study provides evidence of an association between the plasma levels of NfL and white matter involvement in behavioral variant FTD (bvFTD) by relating plasma concentration of NfL to diffusion tensor imaging (DTI) metrics in a group of 20 bvFTD patients. The results of both voxel-wise and tract specific analysis showed that increased plasma NfL concentration is associated with a reduction in fractional anisotropy (FA) in a widespread set of white matter tracts including the superior longitudinal fasciculus, the fronto-occipital fasciculus the anterior thalamic radiation and the dorsal cingulum bundle. Plasma NfL concentration also correlated with cortical thinning in a portion of the right medial prefrontal cortex and of the right lateral orbitofrontal cortex. These results support the hypothesis that blood NfL levels reflect the global level of neurodegeneration in bvFTD and help to advance our understanding of the association between this blood biomarker for FTD and the disease process. p { margin-bottom: 0.1in; direction: ltr; color: #000000; line-height: 115%; text-align: left; orphans: 2; widows: 2; background: transparent } p.western { font-family: "Liberation Serif", serif; font-size: 12pt; so-language: en-US } p.cjk { font-family: "Noto Serif CJK SC"; font-size: 12pt; so-language: zh-CN } p.ctl { font-family: "Lohit Devanagari"; font-size: 12pt; so-language: hi-IN } a:link { color: #0000ff; text-decoration: underli

Background: Progressive supranuclear palsy (PSP) is difficult to diagnose accurately. The recently developed tau PET tracers may improve the diagnostic work-up of PSP. Methods: Regional tau accumulation was studied using 18F-AV-1451 PET in 11 patients with PSP and 11 age-matched healthy controls in the Swedish BioFinder study. Results: 18F-AV-1451 standard uptake volume ratios were significantly higher in the basal ganglia in PSP patients when compared with controls (globus pallidus 1.75 vs 1.50; putamen 1.51 vs 1.35). Retention in the basal ganglia was correlated with age in both groups (r=.43-.78, P

The global extraction of forest and water resources has led to habitat degradation, biodiversity loss, and declines in ecosystem services. As a consequence, ecological restoration has become a glob ...

Neutropenias (NPs), being acute and often transient, or chronic, range from life-threatening conditions with very low absolute neutrophil blood counts (ANC) to disorders characterized by only mild NP and of no obvious significance for health. Many are caused by genetic variations/mutations, e.g. the benign familial NP and the chronic severe NPs (e.g. Kostmann disease). Some of the latter are associated with various bodily malformations. Many of the mild-to-moderate NPs are signs of underlying disorders that need specialized treatments (e.g. HIV, hepatitis, autoimmune disorders, the large granular lymphocyte syndrome). We provide here means for the evaluation of a previously unknown NP, suggest a triage and treatments.

Objective: We describe an Iraqi family with two recessive movement disorders, leukoencephalopathy with ataxia caused by CLCN2 mutations (LKPAT) and autosomal recessive spastic paraplegia 56 (SPG56) caused by mutations in CYP2U1. Methods: Members of an Iraqi family underwent structured interviews and neurological examination. Neuroimaging and whole exome sequencing were performed, and medical records reviewed. Results: Two (II:2, II:4; Figure) out of four siblings examined had spastic paraplegia, cognitive impairment, bladder and bowel dysfunction and gait ataxia. The parents were consanguineous and clinically unaffected. Brain MRI showed T2-weighted hyperintensities and T1-weighted hypointensities in the internal capsules, cerebral peduncles, pyramidal tracts and middle cerebellar peduncles. Both affected patients were homozygous for CYP2U1 c.947A>T p.(Asp316Val), a known cause for SPG56. However, both were also homozygous for a novel CLCN2 c.607G>T, p.(Gly203Cys) variant, classified as a variant of unknown significance. Genetic testing of 4 additional family members revealed homozygosity for the CLCN2 variant also in II:1 whom we initially considered unaffected. Both II:1 and II:4 were infertile, and review of the literature revealed one reported case with LKPAT and azoospermia. II:1 had been examined with testicular biopsy, showing incomplete maturation arrest in spermatogenesis. On clinical examination we found mild memory impairment and hand tremor. MRI showed similar changes to his siblings. Conclusions: We consider the homozygous CLCN2 mutation c.607G>T, p.(Gly203Cys) pathogenic because of the typical neuroradiological and clinical findings in this family. New Generation Sequencing can detect co-occurrence of genetic disorders. Considerable workup can be required to determine the pathogenicity of novel variants. (Less)

ATENCIÓ: la correcció està també al DDD, cal relacionar??? https://ddd.uab.cat/record/226203 Altres ajuts: The following studies and consortia have contributed to this manuscript. Amsterdam dementia Cohort (ADC): Research of the Alzheimer center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). 100-Plus study: We are grateful for the collaborative efforts of all participating centenarians and their family members and/or relations. This work was supported by Stichting Alzheimer Nederland (WE09.2014-03), Stichting Diorapthe, horstingstuit foundation, Memorabel (ZonMW projectnumber 733050814) and Stichting VUmc Fonds. Genotyping of the 100-Plus Study was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). German Study on Ageing, Cognition and Dementia in Primary Care Patients (AgeCoDe): This study/publication is part of the German Research Network on Dementia (KND), the German Research Network on Degenerative Dementia (KNDD; German Study on Ageing, Cognition and Dementia in Primary Care Patients; AgeCoDe), and the Health Service Research Initiative (Study on Needs, health service use, costs and health-related quality of life in a large sample of oldest-old primary care patients (85+; AgeQualiDe)) and was funded by the German Federal Ministry of Education and Research (grants KND: 01GI0102, 01GI0420, 01GI0422, 01GI0423, 01GI0429, 01GI0431, 01GI0433, 01GI0434; grants KNDD: 01GI0710, 01GI0711, 01GI0712, 01GI0713, 01GI0714, 01GI0715, 01GI0716; grants Health Service Research Initiative: 01GY1322A, 01GY1322B, 01GY1322C, 01GY1322D, 01GY1322E, 01GY1322F, 01GY1322G). Alfredo Ramirez was partly supported by the ADAPTED consortium: Alzheimer's disease Apolipoprotein Pathology for Treatment Elucidation and Development, which has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 115975. Brain compendium: This work was funded by the UK Medical Research Council (13044). P.F.C. is a Wellcome Trust principal Fellow (212219/Z/18/Z) and a UK NIHR Senior Investigator, who receives support from the Medical Research Council Mitochondrial Biology Unit (MC_UU_00015/9), and the National Institute for Health Research (NIHR) Biomedical Research Centre based at Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, or the Department of Health.Clinical AD, Sweden: We would like to thank UCL Genomics for performing the genotyping analyses. Danish data: The studies behind the Danish long-lived cases received funding from The National Program for Research Infrastructure 2007 (grant no. 09-063256), the Danish Agency for Science Technology and Innovation, the Velux Foundation, the US National Institute of Health (P01 AG08761), the Danish Agency for Science, Technology and Innovation/The Danish Council for Independent Research (grant no. 11-107308), the European Union's Seventh Framework Programme (FP7/2007-2011) under grant agreement no. 259679, the INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N. (by EU funds from the European Regional Development Fund), the CERA Foundation (Lyon), the AXA Research Fund, Paris, and The Health Foundation (Helsefonden), Copenhagen, Denmark. The GOYA study was conducted as part of the activities of the Danish Obesity Research Centre (DanORC, www.danorc.dk) and The MRC centre for Causal Analyses in Translational Epidemiology (MRC CAiTE). The genotyping for GOYA was funded by the Wellcome Trust (WT 084762). GOYA is a nested study within The Danish National Birth Cohort which was established with major funding from the Danish National Research Foundation. Additional support for this cohort has been obtained from the Pharmacy Foundation, the Egmont Foundation, The March of Dimes Birth Defects Foundation, the Augustinus Foundation, and the Health Foundation. Fundació ACE (FACE): We would like to thank patients and controls who participated in this project. We are indebted to Trinitat Port-Carbó and her family for their support of Fundació ACE research programs. Fundació ACE collaborates with the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, Spain) and is one of the participating centers of the Dementia Genetics Spanish Consortium (DEGESCO). Agustín Ruiz has received support from the EU/EFPIA Innovative Medicines Initiative Joint Undertaking ADAPTED Grant No. 115975 and by grants PI13/02434 and PI16/01861. Acción Estratégica en Salud, integrated in the Spanish National R + D + I Plan and financed by ISCIII (Instituto de Salud Carlos III)-Subdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER- "Una manera de Hacer Europa"), by Fundación bancaria "La Caixa" and Grifols SA (GR@ACE project). Genetics of Healthy Ageing Study (GEHA - NL): The work described in this paper was funded mainly by the EU GEHA Project contract no. LSHM-CT-2004-503-270. Gothenburg Birth Cohort (GBC) Studies: We would like to thank UCL Genomics for performing the genotyping analyses. The studies were supported by The Stena Foundation, The Swedish Research Council (2015-02830, 2013-8717), The Swedish Research Council for Health, Working Life and Wellfare (2013-1202, 2005-0762, 2008-1210, 2013-2300, 2013-2496, 2013-0475), The Brain Foundation, Sahlgrenska University Hospital (ALF), The Alzheimer's Association (IIRG-03-6168), The Alzheimer's Association Zenith Award (ZEN-01-3151), Eivind och Elsa K:son Sylvans Stiftelse, The Swedish Alzheimer Foundation. International FTD-Genomics Consortium (IFGC): International FTD-Genomics Consortium (IFGC): The authors thank the IFGC for providing relevant data to support the analyses presented in this manuscript. Further acknowledgments for IFGC (https://ifgcsite.wordpress.com/), e.g. full members list and affiliations, are found in the online supplementary files. IPDGC (​The International Parkinson Disease Genomics Consortium): We also would like to thank all members of the International Parkinson Disease Genomics Consortium (IPDGC). See for a complete overview of members, acknowledgements and funding http://pdgenetics.org/partners. Kompetenznetz Multiple Sklerose (KKNMS): This work was supported by the German Ministry for Education and Research (BMBF) as part of the "German Competence Network Multiple Sclerosis" (KKNMS) (grant nos. 01GI0916 and 01GI0917) and the Munich Cluster for Systems Neurology (SyNergy). TA was supported by the BMBF through the Integrated Network IntegraMent, under the auspices of the e:Med Programme (01ZX1614J). BH was supported by the EU Horizon 2020 project MultipleMS.Longitudinal Aging Study Amsterdam (LASA) is largely supported by a grant from the Netherlands Ministry of Health, Welfare and Sports, Directorate of Long-Term Care. The authors are grateful to all LASA participants, the fieldwork team and all researchers for their ongoing commitment to the study. Leiden Longevity Study: This study was supported by a grant from the Innovation-Oriented Research Program on Genomics (SenterNovem IGE05007), the Centre for Medical Systems Biology, and the Netherlands Consortium for Healthy Ageing (Grant 050-060-810), all in the framework of the Netherlands Genomics Initiative/Netherlands Organization for Scientific Research (NWO) and by Unilever Colworth.Maria Carolina Dalmasso: Georg Forster Research Award (Alexander von Humboldt Foundation). Mayo Clinic AD, DLB, PD, PSP: We thank the patients and their families for their participation, without whom these studies would not have been possible. Funding for this work was supported by National Institute on Aging [RF AG051504 to NET.; U01 AG046139 to NET]; and National Institute of Neurological Disorders and Stroke [R01 NS080820 to NET; P50 NS072187]. The Mayo Clinic is a Lewy Body Dementia Association (LBDA) Research Center of Excellence, American Parkinson Disease Association (APDA) Information and Referral Center and Center for Advanced Research, NINDS Tau Center without Walls (U54-NS100693) and is supported by Mayo Clinic AD and related dementias genetics program, The Little Family Foundation, the Mangurian Foundation for Lewy body research and NINDS R01 NS078086 (to OAR). The PD program at the Mayo Clinic Florida is also supported by the Mayo Clinic Center for Regenerative Medicine, Mayo Clinic Center for Individualized Medicine, Mayo Clinic Neuroscience Focused Research Team (Cecilia and Dan Carmichael Family Foundation, and the James C. and Sarah K. Kennedy Fund for Neurodegenerative Disease Research at Mayo Clinic in Florida), the gift from Carl Edward Bolch, Jr., and Susan Bass Bolch, and The Sol Goldman Charitable Trust. Samples included in this study are from the brain bank at Mayo Clinic in Jacksonville which is supported by CurePSP The online version of this article (10.1007/s00401-019-02026-8) contains supplementary material, which is available to authorized users.

Objectives: The aim of this study was to assess the psychometric properties of a Swedish version of the Hayling test (HT-S) and its clinical utility in a group of patients with different frontotemporal dementia (FTD) syndromes. Early diagnosis of FTD is a challenge and requires a broad arsenal of assessment methods, neuropsychological tests not the least. The Hayling test assesses executive functions including initiation, efficiency and response inhibition. Methods: Seventy-six healthy controls were included as well as patients with the behavioral variant FTD (bvFTD; n = 17), semantic dementia (SD, n = 6), and progressive supranuclear palsy (n = 12). The Color Word Interference Test was administered to examine the construct validity. Results: Age showed a correlation with better performances in younger participants whereas the importance of sex and education were less evident. The split half reliability and internal consistency were equal to, or better, than reported for the original version. The interrater reliability was excellent. The construct validity was supported, nevertheless indicating partly different processes behind the performances of the two tests. The FTD group performed significantly worse than healthy controls on efficiency and response inhibition and there were also significant differences in performances between the syndromes despite small samples. Conclusions: The psychometric properties and clinical utility of the Swedish version are satisfactory for measuring efficiency and response inhibition with results indicating dissimilar profiles in the performances in the different syndromes. These results need to be corroborated in larger samples. (JINS, 2019, 25, 195–203)

Objective Methods To estimate the prevalence of amyloid positivity, defined by positron emission tomography (PET)/cerebrospinal fluid (CSF) biomarkers and/or neuropathological examination, in primary progressive aphasia (PPA) variants. We conducted a meta-analysis with individual participant data from 1,251 patients diagnosed with PPA (including logopenic [lvPPA, n = 443], nonfluent [nfvPPA, n = 333], semantic [svPPA, n = 401], and mixed/unclassifiable [n = 74] variants of PPA) from 36 centers, with a measure of amyloid-beta pathology (CSF [n = 600], PET [n = 366], and/or autopsy [n = 378]) available. The estimated prevalence of amyloid positivity according to PPA variant, age, and apolipoprotein E (ApoE) epsilon 4 status was determined using generalized estimating equation models. Results Interpretation Amyloid-beta positivity was more prevalent in lvPPA (86%) than in nfvPPA (20%) or svPPA (16%; p

Patients with secondary acute myeloid leukemia (AML) often escape inclusion in clinical trials and thus, population-based studies are crucial for its accurate characterization. In this first large population-based study on secondary AML, we studied AML with an antecedent hematological disease (AHD-AML) or therapy-related AML (t-AML) in the population-based Swedish Acute Leukemia Registry. The study included 3,363 adult patients of which 2,474 (73.6%) had de novo AML, 630 (18.7%) AHD-AML, and 259 (7.7%) t-AML. Secondary AML differed significantly compared to de novo AML with respect to age, gender, and cytogenetic risk. Complete remission (CR) rates were significantly lower but early death rates similar in secondary AML. In a multivariable analysis, AHD-AML (HR 1.51; 95% CI 1.26-1.79) and t-AML (1.72; 1.38-2.15) were independent risk factors for poor survival. The negative impact of AHD-AML and t-AML on survival was highly age dependent with a considerable impact in younger patients, but without independent prognostic value in the elderly. Although patients with secondary leukemia did poorly with intensive treatment, early death rates and survival were significantly worse with palliative treatment. We conclude that secondary AML in a population-based setting has a striking impact on survival in younger AML patients, whereas it lacks prognostic value among the elderly patients.

The Nordic network ERMOND, Ecosystem Resilience for Mitigation of Natural Disasters, reviewed information on natural hazards and ecosystem conditions in the Nordic countries. Many natural hazards put pressure on Nordic societies, primarily floods, landslides, storms, snow avalanches and volcanic activity. Intensified land use and predicted climate change are likely to increase the impacts of natural hazards in the future. Ecosystems in good condition have the ability to reduce the impacts of natural hazards. Our study showed, however, that degradation of natural habitats in the Nordic countries may have reduced or even seriously damaged this ability. Nordic disaster risk reduction policies and strategies should recognize this situation and place restoration of degraded ecosystems on the agenda as an integrated part of future disaster risk reduction management in the Nordic countries.

Currently, toxic and carcinogenic hydrazine propellants are commonly used in spacecraft propulsion. These propellants impose distinctive environmental challenges and consequential hazardous conditions. With an increasing level of future space activities and applications, the significance of greener space propulsion becomes even more pronounced. In this article, a selected number of promising green space propellants are reviewed and investigated for various space missions. In-depth system studies in relation to the aforementioned propulsion architectures further unveil possible approaches for advanced green propulsion systems of the future.

The national guidelines for design of silage bunker silo walls are not available today. The present calculation and design is based on previously issued guidelines. These were elaborated to be used in designing silo wall heights of maximum 3 m. There are reasons to believe that these guidelines overestimate the forces and pressures, mainly from silage juice, that are occurring especially for silo walls > 3 m. This could result in over-sizing, material waste and increased investment costs. The aim of the project is to determine silage physical properties of importance for the horizontal wall pressure and evaluate maximum silage juice level of silos with a wall height of 3 m or more. The data will form a basis for new national design guidelines and a revised Swedish Standard. The ultimate goal is to lower the investment costs for silage bunker silos. A pressure profile was acquired by means of transducers mounted on a “ladder rack” placed vertically along the inside silo wall. The pressure on the transducers was recorded by a data acquisition system displaying static and total load (pressures imposed by silage matter and compacting tractor). The silage juice levels were measured by slotted 16 mm steel pipes placed vertically along the silo walls. The level inside the pipe was determined by a measuring stick. Additionally the juice level could be registered in one of the legs of the “ladder rack”. Silage juice level measurement were carried out during two seasons, all together in 24 silos, while pressure profiles were measured during 10 grass and maize harvests in one season, with approximately 400 pressure profiles at each harvest. The static loads were recorded with no tractor present and total loads as a tractor was passing in front of the transducer racks. The difference between the static and the total load was defined as the dynamic load. Preliminary results show that the silage juice level can vary considerably between harvests within the farm due to weather conditions and geographic location in Sweden. Mean of peak levels was approximately 40% of the silage height. A direct relation was found between grass silage juice level and silage total solid content. The silage juice level tends to remain stable during the storage but can be radically redistributed between layers within the silo. Tentative pressure profile results show that the dynamic pressure created by the compacting tractor is largely concentrated to the first half metre below the vehicle when driving 0.1-0.5 m from the silo wall. Pressure measurements after filling the silo show an increase in wall pressure. The pressure profile results are presently under evaluation. Key words: Silo, wall, silage, pressure, force.

elating restoration ecology to policy is one of the aims of the Society for Ecological Restoration and its journal Restoration Ecology. As an interdisciplinary team of researchers in both ecological science and political science, we have struggled with how policy-relevant language is and could be deployed in restoration ecology. Using language in scientific publications that resonates with overarching policy questions may facilitate linkages between researcher investigations and decision-makers' concerns on all levels. Climate change is the most important environmental problem of our time and to provide policymakers with new relevant knowledge on this problem is of outmost importance. To determine whether or not policy-specific language was being included in restoration ecology science, we surveyed the field of restoration ecology from 2008 to 2010, identifying 1,029 articles, which we further examined for the inclusion of climate change as a key element of the research. We found that of the 58 articles with “climate change” or “global warming” in the abstract, only 3 identified specific policies relevant to the research results. We believe that restoration ecologists are failing to include themselves in policy formation and implementation of issues such as climate change within journals focused on restoration ecology. We suggest that more explicit reference to policies and terminology recognizable to policymakers might enhance the impact of restoration ecology on decision-making processes.

Ecological restoration increases, but evaluation of restoration efforts is inadequate because reliable performance indicators are lacking. As plants are important actors in ecological restoration, we suggest that they be used as metres, i.e. phytometers, of restoration success. Phytometer plants are transplanted to different conditions to integrate measures of the prevailing conditions. We analysed 109 studies for the use of phytometers and especially their applicability to evaluate ecological restoration. Most studies employed single species and life-stages and focused on habitat conditions and environmental impacts. Most experiments were conducted on grasslands in moist temperate regions. Growth was the dominant response variable, in long-term studies often combined with reproductive output and plant survival. Only five studies specifically evaluated ecological restoration, implying that its potential is not yet realised. We found phytometers promising in evaluating restoration outcomes given that they are easy to measure, can provide rapid results, and serve as integrative indicators of environmental conditions with the ability of covering many aspects of plant life and ecosystem processes. To evaluate restoration success with high resolution and generality, we suggest a combination of different phytometer species, life-forms and life-stages, and experimental periods >1 year to reduce effects of transplantation and between-year variation and to account for time lags in ecological processes and changes after restoration.

Von Economo neurons (VEN) are bipolar neurons located in the anterior cingulate cortex (ACC) and the frontoinsular cortex (FI), areas affected early in behavioural variant frontotemporal dementia (bvFTD), in which VEN may constitute a selectively vulnerable cellular population. Aim A previous study has shown a selective loss of VEN in FTD above other neurons in the ACC of FTD. The aim of this study was to confirm this finding in a larger cohort, using a different methodology, and to examine VEN loss in relation to neuropathological severity and molecular pathology. Methods VEN and neighbouring neurons (NN) were quantified in layer Va and Vb of the right dorsal anterior cingulate cortex in 21 cases of behavioural variant FTD, 10 cases of Alzheimer's disease (AD) and 10 non-demented controls (NDC). Results A marked VEN reduction was seen in all FTD cases. In the neuropathologically early cases of FTD (n=13), VEN/10000 NN was significantly reduced by 53 % compared with NDC (p

The purpose of the study was to develop a method for analysis of diffusion parameters along white matter (WM) tracts, using spatial normalization based on anatomical landmarks, and to introduce the apparent area coefficient (AAC). The method's applicability was tested in the inferior fronto-occipital fasciculus (IFO) in patients with progressive supranuclear palsy (PSP) and healthy controls (HCs).A framework for analysis of diffusion parameters was developed. Spatial normalization of the tracts was performed using anatomical landmarks, to avoid deformations caused by cerebral atrophy. Initially, 38 HCs were used to optimize a threshold for the minimal size of regions that differ between groups. The fractional anisotropy, mean diffusivity, AAC, and the hemispheric asymmetry index (AI), were compared between 11 PSP patients and 15 HCs.The method was feasible for analysis of PSP patients and HCs. The AI showed that the observed hemispheric asymmetry of AAC was significantly larger in PSP patients compared with HCs in small regions of the IFO.The method was successfully employed for analysis of diffusion parameters along the IFO in a patient group. This method can be potentially useful in studies of WM diseases, with or without cerebral atrophy.

Disinhibition is an important symptom in neurodegenerative diseases. However, the clinico-anatomical underpinnings remain controversial. We explored the anatomical correlates of disinhibition in neurodegenerative disease using the perspective of grey and white matter imaging. Disinhibition was assessed with a neuropsychological test and a caregiver information-based clinical rating scale in 21 patients with prefrontal syndromes due to behavioural variant frontotemporal dementia (n = 12) or progressive supranuclear palsy (n = 9), and healthy controls (n = 25). Cortical thickness was assessed using the Freesurfer software on 3T MRI data. The integrity of selected white matter tracts was determined by the fractional anisotropy (FA) from Diffusion Tensor Imaging. Disinhibition correlated with the cortical thickness of the right parahippocampal gyrus, right orbitofrontal cortex and right insula and the FA of the right uncinate fasciculus and right anterior cingulum. Notably, no relationship was seen with the thickness of ventromedial prefrontal cortex. Our results support an associative model of inhibitory control, distributed in a medial temporal lobe-insular-orbitofrontal network, connected by the intercommunicating white matter tracts. This reconciles some of the divergences among previous studies, but also questions the current conceptualisation of the "prefrontal" syndrome and the central role attributed to the ventromedial prefrontal cortex in inhibitory control.

Aims: Gestational diabetes mellitus affects approximately 7% of all pregnant women. Some of these women develop autoantibodies that are generally characteristic of Type 1 diabetes. Autoantibodies targeting glutamic acid decarboxylase and tyrosine phosphatase-like protein are the most frequently reported. A recently identified autoantigen in Type 1 diabetes is zinc transporter 8. Some reports suggest that the frequency of zinc transporter 8 antibodies is as high as glutamic acid decarboxylase antibodies in Type 1 diabetes and thus a good diagnostic marker for autoimmune diabetes. There are currently no reports of zinc transporter 8 antibodies in gestational diabetes. The aim of this pilot study was to investigate the frequency of zinc transporter 8 antibodies in patients at clinical onset of gestational diabetes mellitus. Methods: Subjects included in this pilot study were all diagnosed with gestational diabetes at Skane University Hospital, Lund, Sweden, 2009-2010 (n = 193). Sera samples were analysed for antibodies using a commercial enzyme-linked immunosorbent assay according to the manufacturers' instructions. Results: We found that 19/193 patients with gestational diabetes, diagnosed in 2009-2010, were positive for at least one autoantibody. Glutamic acid decarboxylase was the most common single autoantibody (52.6%; 10/19), followed by zinc transporter 8 (21.1%; 4/19) and tyrosine phosphatase-like protein (15.8%; 3/19). Combinations of two or more antibodies were rare (10.5%; 2/19). Conclusions: In this study, we found that zinc transporter 8 added 2.1% (4/193) of autoantibody positivity in women with gestational diabetes who were negative for glutamic acid decarboxylase and tyrosine phosphatase-like protein antibodies. Glutamic acid decarboxylase was still the most prevalent autoantibody in gestational diabetes, but, as zinc transporter 8 was present even in the absence of glutamic acid decarboxylase, this autoantibody could be an important independent marker of autoimmunity in gestational diabetes. © 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.

Reutilization of agricultural buildings for rural tourism (RT) is an area that is significantly expanding today. Buildings originally constructed for agricultural production, processing and housing are an essential part of most RT operations, both as a key resource and a significant cost centre. This study compared the perceptions of RT operators about visitors' opinions of buildings with visitors' actual opinions and attempted to identify the building feature preferences of tourists. The empirical evidence was collected using a 0–4 grade Likert-scale questionnaire that was either internet-based or provided in printed form. The results showed that RT operators partially misinterpreted how visitors view and experience reused buildings and the services therein. Although visitors found building technological factors to be less important than operators did, in a comparison of aggregated tourism-related and building-related factors both operators and visitors considered building-related factors to be of higher...

Increasing numbers of horses are being kept for sports and leisure purposes in peri-urban areas throughout the Western world. This expansion of the equestrian sector represents a multifunctional transition, with new production of rural goods and services and increasing influence on land use. In Sweden, the number of horses has increased from 70,000 to approximately 300,000 over the last 30 years. This increase is putting pressure on the traditional Right of Public Access, an old custom allowing the public to walk, cycle or ride on private or state-owned property. This paper analyses multifunctional land use in peri-urban areas in order to provide a deeper understanding of the potential conflicts arising due to the expanding equine sector and to assess how these can affect the Swedish right of public access and spatial planning. A survey of horse riders and landowners in three peri-urban regions of Sweden revealed that these groups differ in their attitudes towards the Right of Public Access. The data also showed that the expanding equine sector is generating new demands on rural areas and there are questions regarding how the current system of open accessibility can meet the increasing market for equestrian leisure activities. The main conclusion is that there seems to be a strong need for intervention and deliberate creation of new ways of handling the accessibility question, where both a bottom-up and top-down approach may be useful.

Despite the recognized importance of reservoirs and dams, global datasets describing their characteristics and geographical distribution are largely incomplete. To enable advanced assessments of the role and effects of dams within the global river network and to support strategies for mitigating ecohydrological and socioeconomic costs, we introduce here the spatially explicit and hydrologically linked Global Reservoir and Dam database (GRanD). As of early 2011, GRanD contains information regarding 6862 dams and their associated reservoirs, with a total storage capacity of 6197 km3. On the basis of these records, we estimate that about 16.7 million reservoirs larger than 0.01 ha – with a combined storage capacity of approximately 8070 km3 – may exist worldwide, increasing Earth's terrestrial surface water area by more than 305 000 km2. We find that 575 900 river kilometers, or 7.6% of the world's rivers with average flows above 1 cubic meter per second (m3 s−1), are affected by a cumulative upstream reservoir capacity that exceeds 2% of their annual flow; the impact is highest for large rivers with average flows above 1000 m3 s−1, of which 46.7% are affected. Finally, a sensitivity analysis suggests that smaller reservoirs have substantial impacts on the spatial extent of flow alterations despite their minor role in total reservoir capacity. Read More: http://www.esajournals.org/doi/abs/10.1890/100125

The process of measuring in software engineering has already been standardized in the ISO/IEC 15939 standard, where activities related to identifying, creating, and evaluating of measures are described. In the process of measuring software entities, however, an organization usually needs to create custom measurement systems, which are intended to collect, analyze, and present data for a specific purpose. In this paper, we present a proven industrial process for developing measurement systems including the artifacts and deliverables important for a successful deployment of measurement systems in industry. The process has been elicited during a case study at Ericsson and is used in the organization for over 3 years when the paper was written. The process is supported by a framework that simplifies the implementation of the measurement systems and shortens the time from the initial idea to a working measurement system by the factor of 5 compared with using a standard development process not tailored for measurement systems. Copyright © 2010 John Wiley & Sons, Ltd.

Multiple system atrophy (MSA) is a Parkinson's Disease (PD)-like alpha-synucleinopathy clinically characterized by dysautonomia, parkinsonism, cerebellar ataxia, and pyramidal signs in any combination. We aimed to determine whether the clinical presentation of MSA as well as diagnostic and therapeutic strategies differ across Europe and Israel. In 19 European MSA Study Group centres all consecutive patients with a clinical diagnosis of MSA were recruited from 2001 to 2005. A standardized minimal data set was obtained from all patients. Four-hundred thirty-seven MSA patients from 19 centres in 10 countries were included. Mean age at onset was 57.8 years; mean disease duration at inclusion was 5.8 years. According to the consensus criteria 68% were classified as parkinsonian type (MSA-P) and 32% as cerebellar type (MSA-C) (probable MSA: 72%, possible MSA: 28%). Symptomatic dysautonomia was present in almost all patients, and urinary dysfunction (83%) more common than symptomatic orthostatic hypotension (75%). Cerebellar ataxia was present in 64%, and parkinsonism in 87%, of all cases. No significant differences in the clinical presentation were observed between the participating countries. In contrast, diagnostic work up and therapeutic strategies were heterogeneous. Less than a third of patients with documented orthostatic hypotension or neurogenic bladder disturbance were receiving treatment. This largest clinical series of MSA patients reported so far shows that the disease presents uniformly across Europe. The observed differences in diagnostic and therapeutic management including lack of therapy for dysautonomia emphasize the need for future guidelines in these areas. (C) 2010 Movement Disorder Society