Parkinsonism in Gaucher's disease type 1: ten new cases and a review of the literature

Parkinsonism has been described in patients with Gaucher's disease (GD). We reviewed the 10 cases of patients with both parkinsonism and GD recorded in the French national GD registry, as well as 49 previously published cases. Relative to the general population, parkinsonism in GD patients (1) was more frequent, (2) occurred at an earlier age, (3) responded less well to levodopa, and (4) was more frequently associated with signs of cortical dysfunction. Enzyme replacement therapy (ERT) and substrate reduction therapy (SRT) were ineffective on GD-associated parkinsonism, suggesting that parkinsonism itself is not an indication for ERT or SRT in this setting.

Consistent Layout for Thematic Software Maps

Software visualizations can provide a concise overview of a complex software system. Unfortunately, since software has no physical shape, there is no “natural“ mapping of software to a two-dimensional space. As a consequence most visualizations tend to use a layout in which position and distance have no meaning, and consequently layout typical diverges from one visualization to another. We propose a consistent layout for software maps in which the position of a software artifact reflects its \emph{vocabulary}, and distance corresponds to similarity of vocabulary. We use Latent Semantic Indexing (LSI) to map software artifacts to a vector space, and then use Multidimensional Scaling (MDS) to map this vector space down to two dimensions. The resulting consistent layout allows us to develop a variety of thematic software maps that express very different aspects of software while making it easy to compare them. The approach is especially suitable for comparing views of evolving software, since the vocabulary of software artifacts tends to be stable over time.

Epidemiology of secondary leukemia with reference to chromosomal abnormalities

Secondary acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) have been recognized as one of the most feared long-term complications of cancer therapy. The aim of this case-control study was to determine the prevalence of chromosomal abnormalities and family history of cancer among secondary AML/MDS cases and de novo AML/MDS controls. Study population were 332 MD Anderson Cancer Center patients who were registered between 1986 and 1994. Cases were patients who had a prior invasive cancer before diagnoses of AML/MDS and controls were de novo AML/MDS. Cases (166) and controls (166) were frequency matched on age $\pm$5 years, sex and year of diagnosis of leukemia. Cytogenetic data were obtained from the leukemia clinic database of MD Anderson Cancer Center and data on family history of cancer and other risk factors were abstracted from the patients' medical record. The distribution of AML and MDS among cases was 58% and 42% respectively and among controls 67% and 33% respectively. Prevalence of chromosomal abnormalities were observed more frequently among cases than controls. Reporting of family history of cancer were similar among both groups. Univariate analysis revealed an odds ratio (OR) of 2.8 (95% CI 1.5-5.4) for deletion of chromosome 7, 1.9 (95% CI 0.9-3.8) for deletion of chromosome 5, 2.3 (95% CI 0.8-6.2) for deletion of 5q, 2.0 (95% CI 1.0-4.2) for trisomy 8, 1.3 (95% CI 0.8-2.1) for chromosomal abnormalities other than chromosome 5 or 7 and 1.3 (95% CI 0.8-2.0) for family history of cancer in a first degree relative. The OR remained significant for deletion of chromosome 7 (2.3, 95% CI 1.1-4.8) after adjustment for age, alcohol, smoking, occupation related to chemical exposure and family history of cancer in a first degree relative. Of the 166 secondary AML/MDS patients 70% had a prior solid tumor and 30% experienced hematological cancers. The most frequent cancers were breast (21.1%), non-Hodgkin lymphoma (13.3%), Hodgkin's disease (10.2%), prostate (7.2%), colon (6%), multiple myeloma (3.6%) and testes (3.0%). The majority of these cancer patients were treated with chemotherapy or radiotherapy or both. Abnormalities of chromosome 5 or 7 were found to be more frequent in secondary AML/MDS patients with prior hematological cancer than patients with prior solid tumors. Median time to develop secondary AML/MDS was 5 years. However, secondary AML/MDS among patients who received chemotherapy and had a family history of cancer in a first degree relative occurred earlier (median 2.25 $\pm$ 0.9 years) than among patients without such family history (median 5.50 $\pm$ 0.18 years) (p $<$.03). The implication of exposure to chemotherapy among patients with a family history of cancer needs to be further investigated. ^

Le temps des hommes doubles. Les arrangements face à l’occupation, de la Révolution française à la guerre de 1870

Le temps des hommes doubles : Louis Aragon a désigné ainsi la séparation voire l’opposition entre l’homme social et l’homme privé dans la société capitaliste. Pour les auteurs réunis ici, il s’agit plutôt de signifier qu’au temps de la souveraineté nationale en armes, dès lors que sont plus rigoureusement assignées aux soldats et aux citoyens à la fois une « identité » et une « cause » supposées dépasser leur état civil et leurs intérêts particuliers, l’occupation militaire multiplie, dans la recherche d’accommodements entre les deux camps, les tensions et les combinaisons possibles entre fonctions ou statuts publics, sociabilités et influences locales, opinions et besoins. Pour caractériser les évolutions qui ont eu lieu entre les guerres déclarées par la France à l’Autriche en 1792 et à la Prusse en 1870, le présent livre met l’accent sur trois thèmes. Il traite d’abord des enjeux politiques et administratifs de l’occupation, parmi lesquels la neutralité, son devenir en tant que concept dans les relations internationales, et le positionnement des États neutres dans des conflits où l’on s’efforce de mobiliser aussi les opinions publiques. L’attention se porte ensuite sur les armées occupantes. Quelle que soit la part d’idéologie que l’autorité politique introduit dans leurs missions, la première de ces missions est de garantir leur propre sécurité. La recherche des accommodements ou le constat de l’extrême difficulté d’en trouver sont enfin abordés du point de vue des sociétés en proie à l’occupation. Dans ces situations où le présent peut être vécu et interprété en fonction d’une mémoire individuelle et collective d’expériences antérieures, le rôle joué par les occupants ne se réduit pas à la brutalité de la soldatesque et à l’exploitation économique.

Effects of erythropoiesis-stimulating agents on fatigue- and anaemia-related symptoms in cancer patients: systematic review and meta-analyses of published and unpublished data.

Background:Erythropoiesis-stimulating agents (ESAs) reduce the need for red blood cell transfusions; however, they increase the risk of thromboembolic events and mortality. The impact of ESAs on quality of life (QoL) is controversial and led to different recommendations of medical societies and authorities in the USA and Europe. We aimed to critically evaluate and quantify the effects of ESAs on QoL in cancer patients.Methods:We included data from randomised controlled trials (RCTs) on the effects of ESAs on QoL in cancer patients. Randomised controlled trials were identified by searching electronic data bases and other sources up to January 2011. To reduce publication and outcome reporting biases, we included unreported results from clinical study reports. We conducted meta-analyses on fatigue- and anaemia-related symptoms measured with the Functional Assessment of Cancer Therapy-Fatigue (FACT-F) and FACT-Anaemia (FACT-An) subscales (primary outcomes) or other validated instruments.Results:We identified 58 eligible RCTs. Clinical study reports were available for 27% (4 out of 15) of the investigator-initiated trials and 95% (41 out of 43) of the industry-initiated trials. We excluded 21 RTCs as we could not use their QoL data for meta-analyses, either because of incomplete reporting (17 RCTs) or because of premature closure of the trial (4 RCTs). We included 37 RCTs with 10 581 patients; 21 RCTs were placebo controlled. Chemotherapy was given in 27 of the 37 RCTs. The median baseline haemoglobin (Hb) level was 10.1 g dl(-1); in 8 studies ESAs were stopped at Hb levels below 13 g dl(-1) and in 27 above 13 g dl(-1). For FACT-F, the mean difference (MD) was 2.41 (95% confidence interval (95% CI) 1.39-3.43; P<0.0001; 23 studies, n=6108) in all cancer patients and 2.81 (95% CI 1.73-3.90; P<0.0001; 19 RCTs, n=4697) in patients receiving chemotherapy, which was below the threshold (⩾3) for a clinically important difference (CID). Erythropoiesis-stimulating agents had a positive effect on anaemia-related symptoms (MD 4.09; 95% CI 2.37-5.80; P=0.001; 14 studies, n=2765) in all cancer patients and 4.50 (95% CI 2.55-6.45; P<0.0001; 11 RCTs, n=2436) in patients receiving chemotherapy, which was above the threshold (⩾4) for a CID. Of note, this effect persisted when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy. There was some evidence that the MDs for FACT-F were above the threshold for a CID in RCTs including cancer patients receiving chemotherapy with Hb levels below 12 g dl(-1) at baseline and in RCTs stopping ESAs at Hb levels above 13 g dl(-1). However, these findings for FACT-F were not confirmed when we restricted the analysis to placebo-controlled RCTs in patients receiving chemotherapy.Conclusions:In cancer patients, particularly those receiving chemotherapy, we found that ESAs provide a small but clinically important improvement in anaemia-related symptoms (FACT-An). For fatigue-related symptoms (FACT-F), the overall effect did not reach the threshold for a CID.British Journal of Cancer advance online publication, 17 April 2014; doi:10.1038/bjc.2014.171 www.bjcancer.com.

Altered structure of cortical sulci in gilles de la Tourette syndrome: Further support for abnormal brain development.

Gilles de la Tourette syndrome is a neurodevelopmental disorder characterized by the presence of motor and vocal tics. We hypothesized that patients with this syndrome would present an aberrant pattern of cortical formation, which could potentially reflect global alterations of brain development. Using 3 Tesla structural neuroimaging, we compared sulcal depth, opening, and length and thickness of sulcal gray matter in 52 adult patients and 52 matched controls. Cortical sulci were automatically reconstructed and identified over the whole brain, using BrainVisa software. We focused on frontal, parietal, and temporal cortical regions, in which abnormal structure and functional activity were identified in previous neuroimaging studies. Partial correlation analysis with age, sex, and treatment as covariables of noninterest was performed amongst relevant clinical and neuroimaging variables in patients. Patients with Gilles de la Tourette syndrome showed lower depth and reduced thickness of gray matter in the pre- and post-central as well as superior, inferior, and internal frontal sulci. In patients with associated obsessive-compulsive disorder, additional structural changes were found in temporal, insular, and olfactory sulci. Crucially, severity of tics and of obsessive-compulsive disorder measured by Yale Global Tic severity scale and Yale-Brown Obsessive-Compulsive scale, respectively, correlated with structural sulcal changes in sensorimotor, temporal, dorsolateral prefrontal, and middle cingulate cortical areas. Patients with Gilles de la Tourette syndrome displayed an abnormal structural pattern of cortical sulci, which correlated with severity of clinical symptoms. Our results provide further evidence of abnormal brain development in GTS. © 2015 International Parkinson and Movement Disorder Society.

International validation of a behavioral scale in Parkinson's disease without dementia.

The "Ardouin Scale of Behavior in Parkinson's Disease" is a new instrument specifically designed for assessing mood and behavior with a view to quantifying changes related to Parkinson's disease, to dopaminergic medication, and to non-motor fluctuations. This study was aimed at analyzing the psychometric attributes of this scale in patients with Parkinson's disease without dementia. In addition to this scale, the following measures were applied: the Unified Parkinson's Disease Rating Scale, the Montgomery and Asberg Depression Rating Scale, the Lille Apathy Rating Scale, the Bech and Rafaelsen Mania Scale, the Positive and Negative Syndrome Scale, the MacElroy Criteria, the Patrick Carnes criteria, the Hospital Anxiety and Depression Scale, and the Mini-International Neuropsychiatric Interview. Patients (n = 260) were recruited at 13 centers across four countries (France, Spain, United Kingdom, and United States). Cronbach's alpha coefficient for domains ranged from 0.69 to 0.78. Regarding test-retest reliability, the kappa coefficient for items was higher than 0.4. For inter-rater reliability, the kappa values were 0.29 to 0.81. Furthermore, most of the items from the Ardouin Scale of Behavior in Parkinson's Disease correlated with the corresponding items of the other scales, depressed mood with the Montgomery and Asberg Depression Rating Scale (ρ = 0.82); anxiety with the Hospital Anxiety and Depression Scale-anxiety (ρ = 0.56); apathy with the Lille Apathy Rating Scale (ρ = 0.60). The Ardouin Scale of Behavior in Parkinson's disease is an acceptable, reproducible, valid, and precise assessment for evaluating changes in behavior in patients with Parkinson's disease without dementia. © 2015 International Parkinson and Movement Disorder Society.

Real-Time Localization Using Software Defined Radio

Service providers make use of cost-effective wireless solutions to identify, localize, and possibly track users using their carried MDs to support added services, such as geo-advertisement, security, and management. Indoor and outdoor hotspot areas play a significant role for such services. However, GPS does not work in many of these areas. To solve this problem, service providers leverage available indoor radio technologies, such as WiFi, GSM, and LTE, to identify and localize users. We focus our research on passive services provided by third parties, which are responsible for (i) data acquisition and (ii) processing, and network-based services, where (i) and (ii) are done inside the serving network. For better understanding of parameters that affect indoor localization, we investigate several factors that affect indoor signal propagation for both Bluetooth and WiFi technologies. For GSM-based passive services, we developed first a data acquisition module: a GSM receiver that can overhear GSM uplink messages transmitted by MDs while being invisible. A set of optimizations were made for the receiver components to support wideband capturing of the GSM spectrum while operating in real-time. Processing the wide-spectrum of the GSM is possible using a proposed distributed processing approach over an IP network. Then, to overcome the lack of information about tracked devices’ radio settings, we developed two novel localization algorithms that rely on proximity-based solutions to estimate in real environments devices’ locations. Given the challenging indoor environment on radio signals, such as NLOS reception and multipath propagation, we developed an original algorithm to detect and remove contaminated radio signals before being fed to the localization algorithm. To improve the localization algorithm, we extended our work with a hybrid based approach that uses both WiFi and GSM interfaces to localize users. For network-based services, we used a software implementation of a LTE base station to develop our algorithms, which characterize the indoor environment before applying the localization algorithm. Experiments were conducted without any special hardware, any prior knowledge of the indoor layout or any offline calibration of the system.

Real-time localization using software defined radio

Service providers make use of cost-effective wireless solutions to identify, localize, and possibly track users using their carried MDs to support added services, such as geo-advertisement, security, and management. Indoor and outdoor hotspot areas play a significant role for such services. However, GPS does not work in many of these areas. To solve this problem, service providers leverage available indoor radio technologies, such as WiFi, GSM, and LTE, to identify and localize users. We focus our research on passive services provided by third parties, which are responsible for (i) data acquisition and (ii) processing, and network-based services, where (i) and (ii) are done inside the serving network. For better understanding of parameters that affect indoor localization, we investigate several factors that affect indoor signal propagation for both Bluetooth and WiFi technologies. For GSM-based passive services, we developed first a data acquisition module: a GSM receiver that can overhear GSM uplink messages transmitted by MDs while being invisible. A set of optimizations were made for the receiver components to support wideband capturing of the GSM spectrum while operating in real-time. Processing the wide-spectrum of the GSM is possible using a proposed distributed processing approach over an IP network. Then, to overcome the lack of information about tracked devices’ radio settings, we developed two novel localization algorithms that rely on proximity-based solutions to estimate in real environments devices’ locations. Given the challenging indoor environment on radio signals, such as NLOS reception and multipath propagation, we developed an original algorithm to detect and remove contaminated radio signals before being fed to the localization algorithm. To improve the localization algorithm, we extended our work with a hybrid based approach that uses both WiFi and GSM interfaces to localize users. For network-based services, we used a software implementation of a LTE base station to develop our algorithms, which characterize the indoor environment before applying the localization algorithm. Experiments were conducted without any special hardware, any prior knowledge of the indoor layout or any offline calibration of the system.

Earth system commitments due to delayed mitigation

As long as global CO₂ emissions continue to increase annually, long-term committed Earth system changes grow much faster than current observations. A novel metric linking this future growth to policy decisions today is the mitigation delay sensitivity (MDS), but MDS estimates for Earth system variables other than peak temperature (ΔT max) are missing. Using an Earth System Model of Intermediate Complexity, we show that the current emission increase rate causes a ΔT max increase roughly 3–7.5 times as fast as observed warming, and a millenial steric sea level rise (SSLR) 7–25 times as fast as observed SSLR, depending on the achievable rate of emission reductions after the peak of emissions. These ranges are only slightly affected by the uncertainty range in equilibrium climate sensitivity, which is included in the above values. The extent of ocean acidification at the end of the century is also strongly dependent on the starting time and rate of emission reductions. The preservable surface ocean area with sufficient aragonite supersaturation for coral reef growth is diminished globally at an MDS of roughly 25%–80% per decade. A near-complete loss of this area becomes unavoidable if mitigation is delayed for a few years to decades. Also with respect to aragonite, 12%–18% of the Southern Ocean surface become undersaturated per decade, if emission reductions are delayed beyond 2015–2040. We conclude that the consequences of delaying global emission reductions are much better captured if the MDS of relevant Earth system variables is communicated in addition to current trends and total projected future changes.

Progress in Simulations with Twisted Mass Fermions at the Physical Point

In this contribution, results from Nf = 2 lattice QCD simulations at one lattice spacing using twisted mass fermions with a clover term at the physical pion mass are presented. The mass splitting between charged and neutral pions (including the disconnected contribution) is shown to be around 20(20) MeV. Further, a first measurement using the clover twisted mass action of the average momentum fraction of the pion is given. Finally, an analysis of pseudoscalar meson masses and decay constants is presented involving linear interpolations in strange and charm quark masses. Matching to meson mass ratios allows the calculation of quark mass ratios: ms=ml = 27:63(13), mc=ml = 339:6(2:2) and mc=ms = 12:29(10). From this mass matching the quantities fK = 153:9(7:5) MeV, fD = 219(11) MeV, fDs = 255(12) MeV and MDs = 1894(93) MeV are determined without the application of finite volume or discretization artefact corrections and with errors dominated by a preliminary estimate of the lattice spacing.

Effects of subthalamic nucleus stimulation on cognition and mood in Parkinson’s disease (PD)

Objective: To assess the neuropsychological outcome as a safety measure and quality control in patients with subthalamic nucleus (STN) stimulation for PD. Background: Deep brain stimulation (DBS) is considered a relatively safe treatment used in patients with movement disorders. However, neuropsychological alterations have been reported in patients with STN DBS for PD. Cognition and mood are important determinants of quality of life in PD patients and must be assessed for safety control. Methods: Seventeen consecutive patients (8 women) who underwent STN DBS for PD have been assessed before and 4 months after surgery. Besides motor symptoms (UPDRS-III), mood (Beck Depression Inventory, Hamilton Depression Rating Scale) and neuropsychological aspects, mainly executive functions, have been assessed (mini mental state examination, semantic and phonematic verbal fluency, go-no go test, stroop test, trail making test, tests of alertness and attention, digit span, wordlist learning, praxia, Boston naming test, figure drawing, visual perception). Paired t-tests were used for comparisons before and after surgery. Results: Patients were 61.6±7.8 years old at baseline assessment. All surgeries were performed without major adverse events. Motor symptoms ‘‘on’’ medication remained stable whereas they improved in the ‘‘off’’ condition (p<0.001). Mood was not depressed before surgery and remained unchanged at follow-up. All neuropsychological assessment outcome measures remained stable at follow-up with the exception of semantic verbal fluency and wordlist learning. Semantic verbal fluency decreased by 21±16% (p<0.001) and there was a trend to worse phonematic verbal fluency after surgery (p=0.06). Recall of a list of 10 words was worse after surgery only for the third attempt of recall (13%, p<0.005). Conclusions: Verbal fluency decreased in our patients after STN DBS, as previously reported. The procedure was otherwise safe and did not lead to deterioration of mood.