A proposal for a comprehensive grading of Parkinson's disease severity combining motor and non-motor assessments: meeting an unmet need.

Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification

Sur des spécimens historiques inédits d’arthropodes marins des Calcaires Lithographiques de Solnhofen et Nusplingen (Jurassique supérieur, Allemagne) conservés au Muséum national d’Histoire naturelle, Paris

International audiencePlusieurs spécimens fossiles d’arthropodes marins inédits, conservés au Muséum national d’Histoire naturelle à Paris (France) et provenant des Calcaires lithographiques de Solnhofen et de Nusplingen (Jurassique supérieur, Allemagne), sont décrits et illustrés. Nous décrivons notamment des spécimens d’Antrimpos undenarius Schweigert, 2001, d’Eryma modestiforme (Schlotheim, 1822) et de Mecochirus longimanatus (Schlotheim, 1820). Mecochirus foresti Secrétan, 1968 est considéré comme un synonyme plus récent de Mecochirus longimanatus. Une révision des spécimens décrits précédemment est également réalisée. Cet article fournit ainsi de nouvelles informations sur les espèces d’Antrimpos présentes dans les Plattenkalks de Solnhofen et donne un aperçu complet des arthropodes marins fossiles provenant de ces localités et disponibles au MNHN

Sulfur sedimentary processes and fossilization

International audienc

The late stage of Parkinson's –results of a large multinational study on motor and non-motor complications

INTRODUCTION: There is little information on the late stages of parkinsonism. METHODS: We conducted a multicentre study in 692 patients with late stage parkinsonism in six European countries. Inclusion criteria were disease duration of ≥7 years and either Hoehn and Yahr stage ≥4 or Schwab and England score of 50 or less. RESULTS: Average disease duration was 15.4 (SD 7.7) years and mean total UPDRS score was 82.7 (SD 22.4). Dementia according to MDS-criteria was present in 37% of patients. Mean levodopa equivalence dose was 874.1 (SD 591.1) mg/d. Eighty two percent of patients reported falls, related to freezing (16%) or unrelated to freezing (21% of patients) or occurring both related and unrelated to freezing (45%), and were frequent in 26%. Moderate-severe difficulties were reported for turning in bed by 51%, speech by 43%, swallowing by 16% and tremor by 11%. Off-periods occurred in 68% and were present at least 50% of the day in 13%, with morning dystonia occurring in 35%. Dyskinesias were reported by 45% but were moderate or severe only in 7%. Moderate-severe fatigue, constipation, urinary symptoms and nocturia, concentration and memory problems were encountered by more than half of participants. Hallucinations (44%) or delusions (25%) were present in 63% and were moderate-severe in 15%. The association with overall disability was strongest for severity of falls/postural instability, bradykinesia, cognitive score and speech impairment. CONCLUSION: These data suggest that current treatment of late stage parkinsonism in the community remains insufficiently effective to alleviate disabling symptoms in many patients

Caregiver Burden in Late-Stage Parkinsonism and Its Associations

Background: Patients in the late stages of parkinsonism are highly dependent on others in their self-care and activities of daily living. However, few studies have assessed the physical, psychological and social consequences of caring for a person with late-stage parkinsonism. Patients and methods: Five hundred and six patients and their caregivers from the Care of Late Stage Parkinsonism (CLaSP) study were included. Patients’ motor and non-motor symptoms were assessed using the UPDRS and Non-motor symptom scale (NMSS), Neuropsychiatric inventory (NPI-12), and caregivers’ health status using the EQ-5D-3 L. Caregiver burden was assessed by the Zarit Burden Interview (ZBI). Results: The majority of caregivers were the spouse or life partner (71.2%), and were living with the patient at home (67%). Approximately half of caregivers reported anxiety/depression and pain/discomfort (45% and 59% respectively). The factors most strongly associated with caregiver burden were patients’ neuropsychiatric features on the total NPI score (r = 0.38, p < 0.0001), total NMSS score (r = 0.28, p < 0.0001), caring for male patients and patients living at home. Being the spouse, the hours per day assisting and supervising the patient as well as caregivers’ EQ-5D mood and pain scores were also associated with higher ZBI scores (all p < 0.001). Conclusion: The care of patients with late stage parkinsonism is associated with significant caregiver burden, particularly when patients manifest many neuropsychiatric and non-motor features and when caring for a male patient at home

Isotopic ratios of H, C, N, O, and S in comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy)

The apparition of bright comets C/2012 F6 (Lemmon) and C/2014 Q2 (Lovejoy) in March-April 2013 and January 2015, combined with the improved observational capabilities of submillimeter facilities, offered an opportunity to carry out sensitive compositional and isotopic studies of the volatiles in their coma. We observed comet Lovejoy with the IRAM 30m telescope between 13 and 26 January 2015, and with the Odin submillimeter space observatory on 29 January - 3 February 2015. We detected 22 molecules and several isotopologues. The H$_2^{16}$O and H$_2^{18}$O production rates measured with Odin follow a periodic pattern with a period of 0.94 days and an amplitude of ~25%. The inferred isotope ratios in comet Lovejoy are $^{16}$O/$^{18}$O = 499 $\pm$ 24 and D/H = 1.4 $\pm$ 0.4 $\times 10^{-4}$ in water, $^{32}$S/$^{34}$S = 24.7 $\pm$ 3.5 in CS, all compatible with terrestrial values. The ratio $^{12}$C/$^{13}$C = 109 $\pm$ 14 in HCN is marginally higher than terrestrial and $^{14}$N/$^{15}$N = 145 $\pm$ 12 in HCN is half the Earth ratio. Several upper limits for D/H or 12C/13C in other molecules are reported. From our observation of HDO in comet C/2014 Q2 (Lovejoy), we report the first D/H ratio in an Oort Cloud comet that is not larger than the terrestrial value. On the other hand, the observation of the same HDO line in the other Oort-cloud comet, C/2012 F6 (Lemmon), suggests a D/H value four times higher. Given the previous measurements of D/H in cometary water, this illustrates that a diversity in the D/H ratio and in the chemical composition, is present even within the same dynamical group of comets, suggesting that current dynamical groups contain comets formed at very different places or times in the early solar system.Comment: Accepted for publication in Astronomy and Astrophysic

Pore Shape Modification of a Microporous Metal-Organic Framework Using High Pressure:Accessing a New Phase with Oversized Guest Molecules

The authors thank the Royal Society of Edinburgh and the Scottish Government for a fellowship to S.A.M. The authors thank EPSRC (EP/J02077X/1) and Leverhulme Trust for a research project grant (RPG-209) for financial support. They also thank the UK Carr Parinello consortium for allocation of computing time on the EPSRC high performance computing resource ARCHER (managed by the Edinburgh Parallel Computing Centre, the EaSTCHEM Research Computing Facility and the University of Edinburgh ECDF facility).Pressures up to 0.8 GPa have been used to squeeze a range of sterically "oversized" C5-C8 alkane guest molecules into the cavities of a small-pore Sc-based metal?organic framework. Guest inclusion causes a pronounced reorientation of the aromatic rings of one-third of the terephthalate linkers, which act as "torsion springs", resulting in a fully reversible change in the local pore structure. The study demonstrates how pressure-induced guest uptake can be used to investigate framework flexibility relevant to "breathing" behavior and to understand the uptake of guest molecules in MOFs relevant to hydrocarbon separation.PostprintPeer reviewe

The Non-Motor Symptoms Scale in Parkinson's disease: validation and use

The Non‐Motor Symptoms Scale (NMSS) was developed and validated in 2007 as the first instrument for the comprehensive assessment of a range of non‐motor symptoms in Parkinson's disease (PD). Thirteen years have elapsed since its introduction and extensive international validation with good psychometric attributes has been carried out. Here, we review the validation data of the NMSS and its cross‐validity with other scales, and describe the key evidence derived from use of the NMSS in clinical studies. To date, over 100 clinical studies and trials have made use of it as an outcome measure, showing consistent and strong correlations between NMSS burden and health‐related quality of life measures. Moreover, the scale has shown to be capable of detecting longitudinal changes in non‐motor symptoms, where studies have shown differential changes over time of several of the NMSS domains. The scale has become a key outcome in several randomized clinical trials. Highlighting the prevalence and importance of non‐motor symptoms to quality of life in patients with PD, the development of NMSS has also been useful in signposting clinical and biomarker based research addressing non‐motor symptoms in PD

Collective physician perspectives on non-oral medication approaches for the management of clinically relevant unresolved issues in Parkinson's disease: Consensus from an international survey and discussion program

Navigate PD was an educational program established to supplement existing guidelines and provide recommendations on the management of Parkinson's disease (PD) refractory to oral/transdermal therapies. It involved 103 experts from 13 countries overseen by an International Steering Committee (ISC) of 13 movement disorder specialists. The ISC identified 71 clinical questions important for device-aided management of PD. Fifty-six experts responded to a web-based survey, rating 15 questions as ‘critically important;’ these were refined to 10 questions by the ISC to be addressed through available evidence and expert opinion. Draft guidance was presented at international/national meetings and revised based on feedback. Key take-home points are: • Patients requiring levodopa &gt;5 times daily who have severe, troublesome ‘off’ periods (&gt;1–2 h/day) despite optimal oral/transdermal levodopa or non-levodopa-based therapies should be referred for specialist assessment even if disease duration is &lt;4 years. • Cognitive decline related to non-motor fluctuations is an indication for device-aided therapies. If cognitive impairment is mild, use deep brain stimulation (DBS) with caution. For patients who have cognitive impairment or dementia, intrajejunal levodopa infusion is considered as both therapeutic and palliative in some countries. Falls are linked to cognitive decline and are likely to become more frequent with device-aided therapies. • Insufficient control of motor complications (or drug-resistant tremor in the case of DBS) are indications for device-aided therapies. Levodopa-carbidopa intestinal gel infusions or subcutaneous apomorphine pump may be considered for patients aged &gt;70 years who have mild or moderate cognitive impairment, severe depression or other contraindications to DBS