Direct observation of geometric-phase interference in dynamics around a conical intersection.

Conical intersections are ubiquitous in chemistry and physics, often governing processes such as light harvesting, vision, photocatalysis and chemical reactivity. They act as funnels between electronic states of molecules, allowing rapid and efficient relaxation during chemical dynamics. In addition, when a reaction path encircles a conical intersection, the molecular wavefunction experiences a geometric phase, which can affect the outcome of the reaction through quantum-mechanical interference. Past experiments have measured indirect signatures of geometric phases in scattering patterns and spectroscopic observables, but there has been no direct observation of the underlying wavepacket interference. Here we experimentally observe geometric-phase interference in the dynamics of a wavepacket travelling around an engineered conical intersection in a programmable trapped-ion quantum simulator. To achieve this, we develop a technique to reconstruct the two-dimensional wavepacket densities of a trapped ion. Experiments agree with the theoretical model, demonstrating the ability of analogue quantum simulators-such as those realized using trapped ions-to accurately describe nuclear quantum effects.

Acute Flaccid Paralysis: The New, The Old, and The Preventable.

Acute flaccid paralysis (AFP) has a changing epidemiology with ongoing polio outbreaks and emerging causes such as nonpolio enteroviruses and West Nile virus (WNV). We report a case of AFP from the Horn of Africa that was initially classified as probable polio but subsequently found to be due to WNV.

Fifteen-year global time series of satellite-derived fine particulate matter.

Ambient fine particulate matter (PM2.5) is a leading environmental risk factor for premature mortality. We use aerosol optical depth (AOD) retrieved from two satellite instruments, MISR and SeaWiFS, to produce a unified 15-year global time series (1998-2012) of ground-level PM2.5 concentration at a resolution of 1° x 1°. The GEOS-Chem chemical transport model (CTM) is used to relate each individual AOD retrieval to ground-level PM2.5. Four broad areas showing significant, spatially coherent, annual trends are examined in detail: the Eastern U.S. (-0.39 ± 0.10 µg m(-3) yr(-1)), the Arabian Peninsula (0.81 ± 0.21 µg m(-3) yr(-1)), South Asia (0.93 ± 0.22 µg m(-3) yr(-1)) and East Asia (0.79 ± 0.27 µg m(-3) yr(-1)). Over the period of dense in situ observation (1999-2012), the linear tendency for the Eastern U.S. (-0.37 ± 0.13 µg m(-3) yr(-1)) agrees well with that from in situ measurements (-0.38 ± 0.06 µg m(-3) yr(-1)). A GEOS-Chem simulation reveals that secondary inorganic aerosols largely explain the observed PM2.5 trend over the Eastern U.S., South Asia, and East Asia, while mineral dust largely explains the observed trend over the Arabian Peninsula.

The Global Adherence Project (GAP): a multicenter observational study on adherence to disease-modifying therapies in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: most disease-modifying therapies (DMTs) for multiple sclerosis (MS) are self-injectable medications that must be taken on an ongoing basis to reduce disease activity. Thus, adherence to therapy becomes an important challenge that must be addressed to maximize benefits of therapy. This study evaluated rates of adherence to prescribed treatment and explored factors affecting adherence amongst patients with relapsing-remitting MS. METHODS: this was an observational, multicenter, multinational, phase 4 study. Patients and physicians received paper questionnaires regarding adherence to DMTs approved at the time of the study, including intramuscular interferon beta-1a (IFNß-1a), subcutaneous IFNß-1a, IFNß-1b, and glatiramer acetate. Quality of life and cognition data also were collected. Multivariate analysis was conducted to identify factors associated with adherence to long-term DMTs. RESULTS: two thousand six hundred and forty-eight patients were studied, revealing an average treatment duration of 31 months. Seventy-five percent of patients (n = 1923) were adherent to therapy. The most common reasons for non-adherence were forgetting to administer the injection (50.2%) and other injection-related reasons (32.0%). Adherent patients reported better quality of life (P < 0.05) and fewer neuropsychological issues (P < 0.001) than non-adherent patients. Adherent patients had significantly shorter duration of disease (P < 0.001) and shorter duration of therapy (P = 0.005) than non-adherent patients. Women were more likely than men to adhere to treatment. CONCLUSION: identifying factors that affect adherence to prescribed treatments is the first step in improving adherence of patients with MS to therapy, thereby helping maximize the benefits of long-term DMTs.

Sex differences in presentation, severity, and management of stroke in a population-based study.

OBJECTIVES: Women may have poorer outcomes after stroke than men because of differences in their acute management. We examined sex differences in presentation, severity, in-hospital treatment, and early mortality in a cohort of first-ever-in-a-lifetime stroke patients. METHODS: Data were collected from May 1, 1996, to April 30, 1999, in the North East Melbourne Stroke Incidence Study. Stroke symptoms, prestroke medical history, in-hospital investigations, admission and discharge medications, initial stroke severity, and 28-day mortality were recorded. Multivariable regression was used to estimate sex differences in treatment, investigations, and 28-day mortality. RESULTS: A total of 1,316 patients were included. Women were older (mean age 76 +/- 0.6 vs 72 +/- 0.6, p < 0.01), had more severe strokes (median NIH Stroke Scale score 6 vs 5, p < 0.01), and more likely to experience loss of consciousness (31% vs 23%, p = 0.003) and incontinence (22% vs 11%, p = 0.01) than men. Women were less often on lipid-lowering therapy on admission. Echocardiography and carotid investigations were less frequently performed in women due to greater age and stroke severity. Women had greater 28-day mortality (32% vs 21%, p < 0.001) and stroke severity (44% vs 36%, p = 0.01) than men, but adjustment for age, comorbidities, and stroke severity (for mortality only) completely attenuated these associations. CONCLUSION: Sex differences seen in this study were mostly explained by women's older age, greater comorbidity, and stroke severity. The reasons for differences according to age may need further examination.

Why do seizures in generalized epilepsy often occur in the morning?

OBJECTIVE: We used transcranial magnetic stimulation to investigate the effect of diurnal variability on cortical excitability in patients with epilepsy. METHODS: Thirty drug-naive patients with epilepsy (20 idiopathic generalized epilepsy [IGE], including 10 juvenile myoclonic epilepsy [JME], and 10 focal epilepsy) and 10 control subjects without epilepsy were studied both early in the morning and late in the afternoon. We measured the mean motor thresholds and constructed recovery curves at short (2-15 msec) and long (50-400 msec) interstimulus intervals. RESULTS: An increase in cortical excitability indicated by decreased short and long intracortical inhibition was observed early in the morning compared to the afternoon in patients with JME. In other IGE syndromes, there was decreased long intracortical inhibition only. No effect was found in subjects with focal epilepsy or controls without epilepsy. CONCLUSION: Cortical excitability measured by transcranial magnetic stimulation increases early in the morning in patients with idiopathic generalized epilepsy, particularly in juvenile myoclonic epilepsy, but not in subjects with focal epilepsy or controls without epilepsy. This may explain the increased seizure susceptibility in this cohort at this time of day.

Sleep deprivation increases cortical excitability in epilepsy: syndrome-specific effects.

OBJECTIVE: To use transcranial magnetic stimulation (TMS) to investigate the hypothesis that sleep deprivation increases cortical excitability in people with epilepsy. METHODS: We performed paired pulse TMS stimulation, using a number of interstimulus intervals (ISIs) on each hemisphere of 30 patients with untreated newly diagnosed epilepsy (15 idiopathic generalized epilepsy [IGE] and 15 focal epilepsy) and on the dominant hemisphere of 13 healthy control subjects, before and after sleep deprivation. RESULTS: Both hemispheres in patients with IGE and the hemisphere ipsilateral to the EEG seizure focus in those with focal epilepsy showed an increase in cortical excitability following sleep deprivation at a number of ISIs. This change in excitability was most prominent in the patients with IGE. Although there were minor changes after sleep deprivation in control subjects and the contralateral hemisphere in the focal epilepsy group seen at the 250-millisecond ISI, it was less than in the other groups. CONCLUSIONS: Sleep deprivation increases cortical excitability in epilepsy; the pattern of change is syndrome dependent.

Progressive dementia after first-ever stroke: a community-based follow-up study.

OBJECTIVES: To examine the risk and determinants of a progressive dementia syndrome and cognitive impairment not dementia (CIND) in community-based nonaphasic first-ever stroke cases 1 year after stroke, relative to a matched community-based stroke-free group. METHODS: Matched cohort design, with cognitive tests given on two occasions 9 months apart to 99 mild-to-moderate first-ever stroke patients and 99 age- and sex-matched people without stroke. At follow-up, progressive dementia or CIND were diagnosed, with judges blinded to stroke/nonstroke status. RESULTS: Progressive dementia was diagnosed in 12.5% of stroke patients and 15.4% of those without strokes (RR 1.1, 95% CI 0.5 to 2.2, p = 0.85). CIND was diagnosed in 37.5% of stroke patients and 17.6% of participants without strokes (RR 2.1, 95% CI 1.2 to 3.4, p = 0.003). In multivariable regression, age (p = 0.04) and baseline cognition (p < 0.001) were independently associated with dementia whereas stroke (p = 0.002), age (p = 0.05), baseline cognition (p = 0.001), and baseline mood (p = 0.03) were independently associated with CIND at follow-up. CONCLUSIONS: In this community-based nonaphasic sample, mild-to moderate first-ever stroke was not associated with the presence of progressive dementia 1 year later, but was clearly associated with a greater risk of cognitive impairment not dementia (CIND). Baseline mood impairment remained independently associated with CIND at 1 year after taking into account stroke, age, and baseline cognitive ability.

Informal care for stroke survivors: results from the North East Melbourne Stroke Incidence Study (NEMESIS).

BACKGROUND AND PURPOSE: Informal caregivers play an important role in the lives of stroke patients, but the cost of providing this care has not been estimated. The purpose of this study was to determine the nature and amount of informal care provided to stroke patients and to estimate the economic cost of that care. METHODS: The primary caregivers of stroke patients registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were interviewed at 3, 6, and 12 months after stroke, and the nature and amount of informal care provided were documented. The opportunity and replacement costs of informal care for all first-ever-in-a-lifetime strokes (excluding subarachnoid hemorrhages) that occurred in 1997 in Australia were estimated. RESULTS: Among 3-month stroke survivors, 74% required assistance with activities of daily living and received informal care from family or friends. Two thirds of primary caregivers were women, and most primary caregivers (>90%) provided care during family or leisure time. Total first-year caregiver time costs for all first-ever-in-a-lifetime strokes were estimated to be A$21.7 million (opportunity cost approach) or A$42.5 million (replacement cost approach), and the present values of lifetime caregiver time costs were estimated to be A$171.4 million (opportunity cost approach) or A$331.8 million (replacement cost approach). CONCLUSIONS: Informal care for stroke survivors represents a significant hidden cost to Australian society. Because our community is rapidly aging, this informal care burden may increase significantly in the future.

Cost of stroke in Australia from a societal perspective: results from the North East Melbourne Stroke Incidence Study (NEMESIS).

BACKGROUND AND PURPOSE: Accurate information about resource use and costs of stroke is necessary for informed health service planning. The purpose of this study was to determine the patterns of resource use among stroke patients and to estimate the total costs (direct service use and indirect production losses) of stroke (excluding SAH) in Australia for 1997. METHODS: An incidence-based cost-of-illness model was developed, incorporating data obtained from the North East Melbourne Stroke Incidence Study (NEMESIS). The costs of stroke during the first year after stroke and the present value of total lifetime costs of stroke were estimated. RESULTS: The total first-year costs of all first-ever-in-a lifetime strokes (SAH excluded) that occurred in Australia during 1997 were estimated to be A$555 million (US$420 million), and the present value of lifetime costs was estimated to be A$1.3 billion (US$985 million). The average cost per case during the first 12 months and over a lifetime was A$18 956 (US$14 361) and A$44 428 (US$33 658), respectively. The most important categories of cost during the first year were acute hospitalization (A$154 million), inpatient rehabilitation (A$150 million), and nursing home care (A$63 million). The present value of lifetime indirect costs was estimated to be A$34 million. CONCLUSIONS: Similar to other studies, hospital and nursing home costs contributed most to the total cost of stroke (excluding SAH) in Australia. Inpatient rehabilitation accounts for approximately 27% of total first-year costs. Given the magnitude of these costs, investigation of the cost-effectiveness of rehabilitation services should become a priority in this community.

Incidence of the major stroke subtypes: initial findings from the North East Melbourne stroke incidence study (NEMESIS).

BACKGROUND AND PURPOSE: Population-based stroke incidence studies are the only accurate way to determine the number of strokes that occur in a given society. Because the major stroke subtypes have different patterns of incidence and outcome, information on the natural history of stroke subtypes is essential. The purpose of the present study was to determine the incidence and case-fatality rate of the major stroke subtypes in a geographically defined region of Melbourne, Australia. METHODS: All suspected strokes that occurred among 133 816 residents of suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were identified and assessed. Multiple overlapping sources were used to ascertain cases, and standard criteria for stroke and case-fatality were used. Stroke subtypes were defined by CT, MRI, and autopsy. RESULTS: Three hundred eighty-one strokes occurred among 353 persons during the study period, with 276 (72%) being first-ever-in-a-lifetime strokes. Of these, 72.5% (95% CI 67.2% to 77.7%) were cerebral infarction, 14.5% (95% CI 10.3% to 18.6%) were intracerebral hemorrhage, 4.3% (95% CI 1.9% to 6.8%) were subarachnoid hemorrhage, and 8.7% (95% CI 5.4% to 12.0%) were stroke of undetermined type. The 28-day case-fatality rate was 12% (95% CI 7% to 16%) for cerebral infarction, 45% (95% CI 30% to 60%) for intracerebral hemorrhage, 50% (95% CI 22% to 78%) for subarachnoid hemorrhage, and 38% (95% CI 18% to 57%) for stroke of undetermined type. CONCLUSIONS: The overall distribution of stroke subtypes and 28-day case-fatality rates are not significantly different from those of most European countries or the United States. There may, however, be some differences in the incidence of subtypes within Australia.

Prolonged cortical silent period after transcranial magnetic stimulation in generalized epilepsy.

Transcranial magnetic stimulation (TMS) produces a cortical silent period (CSP) during a voluntary contraction. The duration of the CSP was used to assess the level of intracortical inhibition in patients with untreated idiopathic generalized epilepsy (IGE). Mean CSP duration was assessed at three TMS stimuli in 21 patients with IGE compared with 19 normal control subjects. Mean CSP duration was increased at all stimulus intensities, indicating that intracortical inhibition is increased in patients with IGE.

Neurological disability and neurological rehabilitation.

Evidence is increasing that neurorehabilitation lessens patient disability and improves quality of life in both acute and chronic neurological conditions. A focused, multidisciplinary team approach is the key to a successful rehabilitation outcome. The general practitioner will be more closely involved in the rehabilitation process in the future. Patients will be discharged home earlier to complete the acute rehabilitation program. GPs will supervise function over the long term and activate community rehabilitation resources when necessary to maintain patient function. Ideally, rehabilitation services should be available for most patients with neurological disorders, as it is difficult to predict which individual patients will not benefit.

Inter-rater reliability of stroke sub-type classification by neurologists and nurses within a community-based stroke incidence study.

The stroke classification developed for use in the Oxfordshire Community Stroke Project (OCSP) is simple, clinically meaningful and requires no investigations. However, its inter-rater reliability in a community setting is unknown. We aimed to assess the inter-rater reliability of this classification among neurologists and nurses within a community-based stroke incidence study. Fifty-four stroke patients with cerebral infarction who were registered in the North East Melbourne Stroke Incidence Study (NEMESIS) were assigned OCSP classifications by two neurologists and one of seven research nurses. There was moderate agreement between neurologists (kappa = 0.53), fair agreement between neurologist 1 and nurse (kappa = 0.31) and moderate agreement between neurologist 2 and nurse (kappa = 0.45). Disagreement about the neurological signs was an important reason for classification differences. The OCSP classification can be easily applied in a community setting with moderate inter-rater reliability and is thus a useful instrument for commun ity-based epidemiological studies.

Stroke incidence on the east coast of Australia: the North East Melbourne Stroke Incidence Study (NEMESIS).

BACKGROUND AND PURPOSE: Community-based stroke incidence studies are the most accurate way of explaining mortality trends and developing public health policy. The purpose of this study was to determine the incidence of stroke in a geographically defined region of Melbourne, Australia. METHODS: All suspected strokes occurring in a population of 133 816 residents in suburbs north and east of Melbourne, Australia, during a 12-month period of 1996 and 1997 were found and assessed. Multiple overlapping sources were used to ascertain cases, and standard definitions and criteria for stroke and case fatality were used. RESULTS: A total of 381 strokes occurred among 353 people during the study period, 276 (72%) of which were first-ever-in-a-lifetime strokes. The crude annual incidence rate (first-ever strokes) was 206 (95% CI, 182 to 231) per 100 000 per year overall, 195 (95% CI, 161 to 229) for males, and 217 (95% CI, 182 to 252) for females. The corresponding rates adjusted to the "world" population were 100 (95% CI, 80 to 119) overall, 113 (95% CI, 92 to 134) for males, and 89 (95% CI, 70 to 107) for females. The 28-day case fatality rate for first-ever strokes was 20% (95% CI, 16% to 25%). CONCLUSIONS: The incidence rate of stroke in our population-based study is similar to that of many European studies but is significantly higher than that observed on the west coast of Australia.

Intraoperative monitoring to preserve central visual fields during occipital corticectomy for epilepsy.

Photic driving using a flashing strobe light was recorded via intracranial electrodes in two patients with occipital epilepsy being evaluated for surgery. The same technique was used to monitor the visual cortex intraoperatively. Visual evoked potentials (VEPs) were also obtained using the intracranial electrodes in one patient. Preoperative photic driving occurred in a separate location from the cortical areas producing ictal epileptiform activity. VEPs were located in the same site as photic driving. Photic driving was monitored throughout the resection and remained unaffected at the end of each procedure. Postoperative visual field testing in both patients showed preservation of central vision although some reduction in peripheral fields was seen. Intraoperative monitoring of the visual cortex using photic stimulation proved to be a reliable technique for preserving central vision during occipital lobe surgery.

Interrater reliability of the National Institutes of Health Stroke Scale: rating by neurologists and nurses in a community-based stroke incidence study.

The reliability of the National Institutes of Health Stroke Scale (NIHSS) for use by trained neurologists in clinical trials of acute stroke has been established in several hospital-based studies. However, it also has the potential for application in community-based settings and to be used by nonneurologists: issues which have not been explored before. Hence, we aimed to determine the reliability of the NIHSS when administered by research nurses within the existing North Eastern Melbourne Stroke Incidence Study. Using the NIHSS, thirty-one consecutively registered stroke patients were assessed by 2 neurologists and 1 of 2 trained research nurses. The interrater reliability of observations was compared using weighted and unweighted kappa statistics and intraclass correlation coefficients (ICC). There was a high level of agreement for total scores between the 2 neurologists (ICC = 0.95) and between each neurologist and research nurse (ICC = 0.92 and 0.96). While there was moderate to excellent agreement among neurologists and research nurse (weighted kappa > 0.4) for the majority of the NIHSS items, there was poor agreement for the component 'limb ataxia'. Overall, agreement between nurse and neurologist for individual items was not significantly different from agreement between neurologists. It appears that in both hospital and community settings, trained research nurses can administer the NIHSS with a reliability similar to stroke-trained neurologists. This ability could be used to advantage in large community-based trials and epidemiological studies.