Proposal for witnessing non-classical light with the human eye

We give a complete proposal showing how to detect the non-classical nature of photonic states with naked eyes as detectors. The enabling technology is a sub-Poissonian photonic state that is obtained from single photons, displacement operations in phase space and basic non-photon-number-resolving detectors. We present a detailed statistical analysis of our proposal including imperfect photon creation and detection and a realistic model of the human eye. We conclude that a few tens of hours are sufficient to certify non-classical light with the human eye with a p-value of 10%.Comment: 9 pages, 5 figures, accepted versio

Costs of Parkinson's Disease and Antiparkinsonian Pharmacotherapy: An Italian Cohort Study

Objective: Antiparkinsonian pharmacotherapy is costly and the determinants of drug costs in Parkinson's disease (PD) have been poorly investigated. The objective of this study was to investigate the costs of PD and antiparkinsonian drugs in an Italian cohort of patients and identify cost-driving factors of drug therapy. Methods: Seventy outpatients with idiopathic PD were recruited in the Department of Neurology, Napoli University, Italy. Data on resource utilization were collected for 6 months using a bottom-up approach. Clinical status was evaluated using the Unified Parkinson's Disease Rating Scale. Direct and indirect costs were calculated from the societal perspective (figures of year 2009). Independent determinants of total costs and costs of antiparkinsonian drugs were identified using multivariate regression analysis. Results: The total costs of PD were EUR 8,640 (95% CI: EUR 6,700-11,240) per patient over a 6-month period. Direct costs accounted for 70% of the total costs. Antiparkinsonian drugs (EUR 1,450; 95% CI: EUR 1,220-1,760) were the primary component of costs paid by the health insurance (39.6%) and one of the most expensive components of the direct costs (24.0%). The highest copayments made by patients were for antiparkinsonian drugs and medical equipment (58%). Independent determinants of the increased costs of antiparkinsonian pharmacotherapy were younger age and occurrence of motor fluctuations. Conclusions: Antiparkinsonian pharmacotherapy is one of the major cost components of PD-related costs for health insurance. It imposes a considerable economic burden on patients and their families as well. Copyright (C) 2010 S. Karger AG, Base

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

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

Mapping the EQ-5D index by UPDRS and PDQ-8 in patients with Parkinson’s disease

Background: Clinical studies employ the Unified Parkinson’s Disease Rating Scale (UPDRS) to measure the severity of Parkinson’s disease. Evaluations often fail to consider the health-related quality of life (HrQoL) or apply disease-specific instruments. Health-economic studies normally use estimates of utilities to calculate quality-adjusted life years. We aimed to develop an estimation algorithm for EuroQol- 5 dimensions (EQ-5D)-based utilities from the clinical UPDRS or disease-specific HrQoL data in the absence of original utilities estimates. Methods: Linear and fractional polynomial regression analyses were performed with data from a study of Parkinson’s disease patients (n=138) to predict the EQ-5D index values from UPDRS and Parkinson’s disease questionnaire eight dimensions (PDQ-8) data. German and European weights were used to calculate the EQ-5D index. The models were compared by R2, the root mean square error (RMS), the Bayesian information criterion, and Pregibon’s link test. Three independent data sets validated the models. Results: The regression analyses resulted in a single best prediction model (R2: 0.713 and 0.684, RMS: 0.139 and 13.78 for indices with German and European weights, respectively) consisting of UPDRS subscores II, III, IVa-c as predictors. When the PDQ-8 items were utilised as independent variables, the model resulted in an R2 of 0.60 and 0.67. The independent data confirmed the prediction models. Conclusion: The best results were obtained from a model consisting of UPDRS subscores II, III, IVa-c. Although a good model fit was observed, primary EQ-5D data are always preferable. Further validation of the prediction algorithm within large, independent studies is necessary prior to its generalised use

Characteristics of Patients with Late-Stage Parkinsonism who are Nursing Home Residents Compared with those Living at Home

OBJECTIVES: To determine clinical characteristics and treatment complications of patients with late-stage Parkinsonism living in nursing homes compared with those living at home. DESIGN: Cross-sectional analysis. SETTING AND PARTICIPANTS: This study is an analysis of 692 patients with late stage Parkinsonism recruited to an in-depth international study, Care of Late-Stage Parkinsonism (CLaSP). MEASURES: Sociodemographic characteristics were compared between patients who were living in a nursing home (n = 194) and those living at home (n = 498). Clinical assessments included the Unified Parkinson's Disease Rating Scale (UPDRS), the nonmotor symptom scale, the neuropsychiatric inventory, and a structured interview of patients and carers. Predictors of nursing home status were determined in a multivariate analysis. RESULTS: Nursing home placement was strongly associated with more severe cognitive impairment, worse UPDRS motor scores and disability, and with being unmarried and older. Although nursing home residents had significantly higher axial scores, falls were less common. Despite similar levodopa equivalence doses, they had less dyskinesia. Nonmotor symptom burden, particularly delusion, hallucination, and depression scores were higher in nursing home residents, and they were more frequently on psychotropic medication. They had lower rates of dopamine agonist use and lower rates of impulse control disorders. In multivariate analysis, being unmarried, presence of cognitive impairment, worse disease severity as assessed on the UPDRS parts II and III, severity of delusions, and lower rate of dyskinesia were associated with nursing home placement. CONCLUSIONS AND IMPLICATIONS: These clinical characteristics suggest that in patients with Parkinsonsim who are nursing home residents, presence of cognitive impairment and delusions particularly add to the higher overall symptom burden, and more often require specific treatments, including clozapine. Despite similar levodopa equivalent daily dose, motor severity is higher, and dyskinesias, indicative of a response to levodopa, are less common. Falls, however, also occur less commonly, and dopamine agonists are less frequently used, with lower rates of impulse control disorder

An mRNA processing pathway suppresses metastasis by governing translational control from the nucleus

Cancer cells often co-opt post-transcriptional regulatory mechanisms to achieve pathologic expression of gene networks that drive metastasis. Translational control is a major regulatory hub in oncogenesis; however, its effects on cancer progression remain poorly understood. Here, to address this, we used ribosome profiling to compare genome-wide translation efficiencies of poorly and highly metastatic breast cancer cells and patient-derived xenografts. We developed dedicated regression-based methods to analyse ribosome profiling and alternative polyadenylation data, and identified heterogeneous nuclear ribonucleoprotein C (HNRNPC) as a translational controller of a specific mRNA regulon. We found that HNRNPC is downregulated in highly metastatic cells, which causes HNRNPC-bound mRNAs to undergo 3′ untranslated region lengthening and, subsequently, translational repression. We showed that modulating HNRNPC expression impacts the metastatic capacity of breast cancer cells in xenograft mouse models. In addition, the reduced expression of HNRNPC and its regulon is associated with the worse prognosis in breast cancer patient cohorts

Quantifying the profile and progression of impairments, activity, participation, and quality of life in people with Parkinson disease : protocol for a prospective cohort study

Background Despite the finding that Parkinson disease (PD) occurs in more than one in every 1000 people older than 60 years, there have been few attempts to quantify how deficits in impairments, activity, participation, and quality of life progress in this debilitating condition. It is unclear which tools are most appropriate for measuring change over time in PD. Methods and design This protocol describes a prospective analysis of changes in impairments, activity, participation, and quality of life over a 12 month period together with an economic analysis of costs associated with PD. One-hundred participants will be included, provided they have idiopathic PD rated I-IV on the modified Hoehn &amp; Yahr (1967) scale and fulfil the inclusion criteria. The study aims to determine which clinical and economic measures best quantify the natural history and progression of PD in a sample of people receiving services from the Victorian Comprehensive Parkinson\u27s Program, Australia. When the data become available, the results will be expressed as baseline scores and changes over 3 months and 12 months for impairment, activity, participation, and quality of life together with a cost analysis. Discussion This study has the potential to identify baseline characteristics of PD for different Hoehn &amp; Yahr stages, to determine the influence of disease duration on performance, and to calculate the costs associated with idiopathic PD. Valid clinical and economic measures for quantifying the natural history and progression of PD will also be identified

Quality of Life and Costs in Parkinson's Disease: A Cross Sectional Study in Hungary.

BACKGROUND: Patient reported outcomes and costs of illness are useful to capture some of the multiple effects of a disease and its treatments. Our aim was to assess quality of life (QoL) and costs of Parkinson's disease (PD) in Hungary, and to analyze their associations. METHODS: A cross-sectional questionnaire survey was conducted in one neurology university clinic. Clinical characteristics, PD related resource utilizations and productivity loss in the past 12 months were recorded; the Hoehn&Yahr (HY) scale, PDQ-39 and EQ-5D questionnaires were applied. Cost calculation was performed from the societal perspective. RESULTS: 110 patients (34.5% female) were involved with mean age of 63.3 (SD = 11.3) and disease duration of 8.2 (SD = 5.8) years. PDQ-39 summary score was 48.1 (SD = 13.4). The average EQ-5D score was 0.59 (SD = 0.28), and was significantly lower than the population norm in age-groups 45-74. The correlation was significant between EQ-5D and PDQ-39 (-0.47, p = 0.000), the HY scale and EQ-5D (-0.3416, p = 0.0008) and PDQ-39 (0.3419, p = 0.0006) scores. The total mean cost was euro6030.2 (SD = 6163.0)/patient/year (direct medical 35.7%, direct non-medical 29.4%, indirect cost 34.9%). A one year increase in disease duration and 0.1 decrease of the EQ-5D utility score increase the yearly costs by 8 to 10%, and 7.8%, respectively. The effect of the PDQ-39 score on total cost was not significant. CONCLUSIONS: Disease severity and public health importance of PD are clearly demonstrated by the magnitude of QoL loss. PD-related costs are substantial, but are much lower in Hungary than in Western European countries. Disease duration and EQ-5D score are significant proxy of costs