Mortality in Levodopa-Treated Parkinson\u27s Disease

Parkinson’s disease (PD) is associated with increased mortality despite many advances in treatment. Following the introduction of levodopa in the late 1960’s, many studies reported improved or normalized mortality rates in PD. Despite the remarkable symptomatic benefits provided by levodopa, multiple recent studies have demonstrated that PD patients continue to die at a rate in excess of their peers. We undertook this retrospective study of 211 deceased PD patients to determine the factors associated with mortality in levodopa-treated PD. Our findings confirm that PD is associated with increased mortality in both men and women. Unlike the majority of other mortality studies, we found that women have a greater reduction in lifespan compared to men. We also found that patients with early onset PD (onset at the age of 50 or before) have reduced survival relative to PD patients with later ages of onset. A final important finding is that survival is equal in PD patients treated with levodopa early (within 2 years or less of PD onset) versus later

The a-axis optical conductivity of detwinned ortho-II YBa_2Cu_3O_6.50

The a-axis optical properties of a detwinned single crystal of YBa_2Cu_3O_6.50 in the ortho II phase (Ortho II Y123, T_c= 59 K) were determined from reflectance data over a wide frequency range (70 - 42 000 cm^-1) for nine temperature values between 28 and 295 K. Above 200 K the spectra are dominated by a broad background of scattering that extends to 1 eV. Below 200 K a shoulder in the reflectance appears and signals the onset of scattering at 400 cm^-1. In this temperature range we also observe a peak in the optical conductivity at 177 cm^-1. Below 59 K, the superconducting transition temperature, the spectra change dramatically with the appearance of the superconducting condensate. Its spectral weight is consistent, to within experimental error, with the Ferrell-Glover-Tinkham (FGT) sum rule. We also compare our data with magnetic neutron scattering on samples from the same source that show a strong resonance at 31 meV. We find that the scattering rates can be modeled as the combined effect of the neutron resonance and a bosonic background in the presence of a density of states with a pseudogap. The model shows that the decreasing amplitude of the neutron resonance with temperature is compensated for by an increasing of the bosonic background yielding a net temperature independent scattering rate at high frequencies. This is in agreement with the experiments.Comment: 13 pages 16 figure

G2019S mutation in the leucine-rich repeat kinase 2 gene is not associated with multiple system atrophy

Multiple system atrophy (MSA) is characterized clinically by Parkinsonism, cerebellar dysfunction, and autonomic impairment. Multiple mutations in the LRRK2 gene are associated with parkinsonian disorders, and the most common one, the G2019S mutation, has been found in ∼1% of sporadic cases of Parkinsonism. In a well-characterized cohort of 136 subjects with probable MSA and 110 neurologically evaluated control subjects, none carried the G2019S mutation. We conclude that the G2019S mutation in the LRRK2 gene is unlikely to be associated with MSA. © 2007 Movement Disorder SocietyPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56014/1/21343_ftp.pd

The GLY2019SER Mutation in LRRK2 is Not Fully Penetrant in Familial Parkinson\u27s Disease: the GenePD Study

Background: We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (LRRK2)-related Parkinson\u27s disease (PD) in a large sample of familial PD. The most frequently seen LRRK2 mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of LRRK2 mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD. Methods: A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different LRRK2 mutations. Penetrance was estimated in families of LRRK2 carriers with consideration of the inherent bias towards increased penetrance in a familial sample. Results: Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 LRRK2 mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the LRRK2 mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-LRRK2-related PD families. Conclusion: Lifetime penetrance of LRRK2 estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained LRRK2 cases, suggesting that inherited susceptibility factors may modify the penetrance of LRRK2 mutations. In addition, the presence of nine PD phenocopies in the LRRK2 families suggests that these susceptibility factors may also increase the risk of non-LRRK2-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for LRRK2 carriers are independent of the factors which increase PD prevalence in men

The Gly2019Ser mutation in LRRK2 is not fully penetrant in familial Parkinson's disease: the GenePD study

<p>Abstract</p> <p>Background</p> <p>We report age-dependent penetrance estimates for leucine-rich repeat kinase 2 (<it>LRRK2</it>)-related Parkinson's disease (PD) in a large sample of familial PD. The most frequently seen <it>LRRK2 </it>mutation, Gly2019Ser (G2019S), is associated with approximately 5 to 6% of familial PD cases and 1 to 2% of idiopathic cases, making it the most common known genetic cause of PD. Studies of the penetrance of <it>LRRK2 </it>mutations have produced a wide range of estimates, possibly due to differences in study design and recruitment, including in particular differences between samples of familial PD versus sporadic PD.</p> <p>Methods</p> <p>A sample, including 903 affected and 58 unaffected members from 509 families ascertained for having two or more PD-affected members, 126 randomly ascertained PD patients and 197 controls, was screened for five different <it>LRRK2 </it>mutations. Penetrance was estimated in families of <it>LRRK2 </it>carriers with consideration of the inherent bias towards increased penetrance in a familial sample.</p> <p>Results</p> <p>Thirty-one out of 509 families with multiple cases of PD (6.1%) were found to have 58 <it>LRRK2 </it>mutation carriers (6.4%). Twenty-nine of the 31 families had G2019S mutations while two had R1441C mutations. No mutations were identified among controls or unaffected relatives of PD cases. Nine PD-affected relatives of G2019S carriers did not carry the <it>LRRK2 </it>mutation themselves. At the maximum observed age range of 90 to 94 years, the unbiased estimated penetrance was 67% for G2019S families, compared with a baseline PD risk of 17% seen in the non-<it>LRRK2</it>-related PD families.</p> <p>Conclusion</p> <p>Lifetime penetrance of <it>LRRK2 </it>estimated in the unascertained relatives of multiplex PD families is greater than that reported in studies of sporadically ascertained <it>LRRK2 </it>cases, suggesting that inherited susceptibility factors may modify the penetrance of <it>LRRK2 </it>mutations. In addition, the presence of nine PD phenocopies in the <it>LRRK2 </it>families suggests that these susceptibility factors may also increase the risk of non-<it>LRRK2</it>-related PD. No differences in penetrance were found between men and women, suggesting that the factors that influence penetrance for <it>LRRK2 </it>carriers are independent of the factors which increase PD prevalence in men.</p

Lawson criterion for ignition exceeded in an inertial fusion experiment

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion