Optical characterisation of micro-fabricated Fresnel zone plates for atomic waveguides.

We optically assess Fresnel zone plates (FZPs) that are designed to guide cold atoms. Imaging of various ring patterns produced by the FZPs gives an average RMS error in the brightest part of the ring of 3% with respect to trap depth. This residue is attributed to the imaging system, incident beam shape and FZP manufacturing tolerances. Axial propagation of the potentials is presented experimentally and through numerical simulations, illustrating prospects for atom guiding without requiring light sheets.

Progesterone and human cognition.

Progesterone is a neurosteroid and a neuroactive steroid, produced primarily by the corpus luteum and the placenta. In some animal models, progesterone affects cognitive performance, and its potential role in human cognition is especially germane to women. This role can be investigated through associations between peripheral concentrations of progesterone in blood or saliva and neuropsychological test results, through differences in cognitive profiles between women using menopausal hormone therapy with and without a progestogen, and through clinical trials. In naturally cycling reproductive-age women and pregnant women, there is no consistent relation between progesterone levels and cognition. In postmenopausal women within 6 years of menopause and not using hormone therapy, progesterone levels are positively associated with verbal memory and global cognition, but reported associations in older postmenopausal women are null. Some observational studies of postmenopausal women using hormone therapy raise concern of a small deleterious cognitive effect of progestogen (medroxyprogesterone acetate was most often reported in these studies), but this association may due to confounding factors. Small, short-term clinical trials of progesterone show no meaningful effect on cognition. The quality of evidence is low, but overall findings do not reveal consistent, clinically important effects of progesterone on cognitive function in women.

Individually modifiable risk factors to ameliorate cognitive aging: a systematic review and meta-analysis.

A number of health and lifestyle factors are thought to contribute to cognitive decline associated with age but cannot be easily modified by the individual patient. We identified 12 individually modifiable interventions that can be implemented during midlife or later with the potential to ameliorate cognitive aging. For ten of these, we used PubMed databases for a systematic review of long-duration (at least 6 months), randomized, controlled trials in midlife and older adults without dementia or mild cognitive impairment with objective measures of neuropsychological performance. Using network meta-analysis, we performed a quantitative synthesis for global cognition (primary outcome) and episodic memory (secondary outcome). Of 1038 publications identified by our search strategy, 24 eligible trials were included in the network meta-analysis. Results suggested that the Mediterranean diet supplemented by olive oil and tai chi exercise may improve global cognition, and the Mediterranean diet plus olive oil and soy isoflavone supplements may improve memory. Effect sizes were no more than small (standardized mean differences 0.11-0.22). Cognitive training may have cognitive benefit as well. Most individually modifiable risk factors have not yet been adequately studied. We conclude that some interventions that can be self-initiated by healthy midlife and older adults may ameliorate cognitive aging.

Three midlife strategies to prevent cognitive impairment due to Alzheimer's disease.

The slow, progressive accumulation of pathology characteristic of Alzheimer's disease is the principal determinant of cognitive decline leading to dementia. Risk-reduction strategies during midlife focus on raising the clinical threshold for the appearance of cognitive symptoms and on reducing the extent of Alzheimer pathology. Best available evidence suggests an approach based on three, conceptually distinct strategies. (1) Raise the threshold for cognitive symptoms by improving brain health. To achieve this goal, the tactic is to reduce cerebrovascular risks mediated by hypertension, diabetes, cigarette smoking, and hyperlipidemia. (2) Raise the threshold for cognitive symptoms by enhancing cognitive reserve. Here, tactics focus on mental stimulation associated with occupation, leisure activities and social engagement. (3) Reduce the burden of Alzheimer pathology. The most promising tactic toward this end is regular aerobic exercise. Tactics in support of strategies to reduce cognitive impairment due to Alzheimer pathology are not yet substantiated by robust, consistent clinical trial evidence. There is pressing need for well-designed pragmatic trials to provide stronger evidence on preventive strategies for late-life cognitive decline and dementia.

Prevention of diseases after menopause.

Women may expect to spend more than a third of their lives after menopause. Beginning in the sixth decade, many chronic diseases will begin to emerge, which will affect both the quality and quantity of a woman's life. Thus, the onset of menopause heralds an opportunity for prevention strategies to improve the quality of life and enhance longevity. Obesity, metabolic syndrome and diabetes, cardiovascular disease, osteoporosis and osteoarthritis, cognitive decline, dementia and depression, and cancer are the major diseases of concern. Prevention strategies at menopause have to begin with screening and careful assessment for risk factors, which should also include molecular and genetic diagnostics, as these become available. Identification of certain risks will then allow directed therapy. Evidence-based prevention for the diseases noted above include lifestyle management, cessation of smoking, curtailing excessive alcohol consumption, a healthy diet and moderate exercise, as well as mentally stimulating activities. Although the most recent publications from the follow-up studies of the Women's Health Initiative do not recommend menopause hormonal therapy as a prevention strategy, these conclusions may not be fully valid for midlife women, on the basis of the existing data. For healthy women aged 50-59 years, estrogen therapy decreases coronary heart disease and all-cause mortality; this interpretation is entirely consistent with results from other randomized, controlled trials and observational studies. Thus. as part of a comprehensive strategy to prevent chronic disease after menopause, menopausal hormone therapy, particularly estrogen therapy may be considered as part of the armamentarium.

Hormone therapy and the risk of stroke: perspectives 10 years after the Women's Health Initiative trials.

Principal findings on stroke from the Women's Health Initiative (WHI) clinical trials of hormone therapy indicate that estrogen, alone or with a progestogen, increases a woman's risk of stroke. These results were not unexpected, and research during the past decade has tended to support these findings. Consistent evidence from clinical trials and observational research indicates that standard-dose hormone therapy increases stroke risk for postmenopausal women by about one-third; increased risk may be limited to ischemic stroke. Risk is not modified by age of hormone initiation or use, or by temporal proximity to menopause, and risk is similar for estrogen plus progestogen and for unopposed estrogen. Limited evidence implies that lower doses of transdermal estradiol (≤50 µg/day) may not alter stroke risk. For women less than 60 years of age, the absolute risk of stroke from standard-dose hormone therapy is rare, about two additional strokes per 10 000 person-years of use; the absolute risk is considerably greater for older women. Other hormonally active compounds - including raloxifene, tamoxifen, and tibolone - can also affect stroke risk.

Hormone therapy, dementia, and cognition: the Women's Health Initiative 10 years on.

Principal findings on dementia from the Women's Health Initiative Memory Study (WHIMS) showed that conjugated equine estrogens plus medroxyprogesterone acetate (CEE/MPA) increase dementia risk in women aged 65 years and above, but not risk of mild cognitive impairment. The dementia finding was unexpected, given consistent observational evidence that associates use of estrogen-containing hormone therapy with reduced risk of Alzheimer's disease. It remains controversial whether hormone use by younger postmenopausal women near the time of menopause reduces dementia risk or whether WHIMS findings should be generalized to younger women. Given the challenges of conducting a primary prevention trial to address that question, it is helpful to consider the impact of hormone therapy on cognitive test performance, particularly verbal memory, for its own sake and as a proxy for dementia risk. The WHI Study of Cognitive Aging (WHISCA) showed that CEE/MPA worsened verbal memory, whereas CEE alone had no influence on cognition. These findings have been replicated in several randomized, clinical trials. The apparent negative effect of CEE/MPA on verbal memory does not appear to be age-dependent. Additional investigations are needed to understand the impact of other hormonally active compounds on dementia and cognitive outcomes.

Distribution of selected virulence genes and antibiotic resistance in Enterococcus species isolated from the South Nation River drainage basin, Ontario, Canada.

AIMS: Isolate and characterize water enterococci from the South Nation River drainage basin, an area dominated by agriculture. METHODS AND RESULTS: A total of 1558 enterococci were isolated from 204 water samples from the South Nation River obtained over a 3-year period. PCR was used to identify isolates to the species level and characterize them for carriage of 12 virulence determinants. Antibiotic resistance was evaluated phenotypically. Enterococcus faecalis (36·4%), Enterococcus faecium (9·3%) and Enterococcus durans (8·5%) were the major enterococci species isolated. Enterococci carrying more than two virulence determinants were more frequently detected in the summer (59·6%) than in other seasons (≤ 37·6%). Very few isolates (≤ 2·0%) were resistant to category I antibiotics ciprofloxacin and vancomycin. CONCLUSIONS: Comparison of major water enterococci species with major faecal enterococci species obtained from various host groups (human, domesticated mammals and birds, wildlife) in this drainage basin suggest that water enterococci may have varied faecal origins. The low level of antibiotic resistance among enterococci suggests that dispersion of antibiotic resistance via waterborne enterococci in this watershed is not significant. SIGNIFICANCE AND IMPACT OF THE STUDY: The data obtained in this study suggests that water enterococci in the SNR have a faecal origin and that their potential impact on public health regarding antibiotic resistance and virulence determinants is minimal.

Age of menopause and impact of climacteric symptoms by geographical region.

OBJECTIVE: To describe differences in the age of onset of menopause and in the prevalence of climacteric symptoms in different geographical areas. DESIGN: Systematic review of published data on onset of menopause and symptoms in Europe, North America, Latin America and Asia. METHODS: We identified publications by searching electronic databases, including MEDLINE (1966-October 2009) and EMBASE (1975-October 2009). Primary search criteria were age of menopause and climacteric symptoms. A sensitive analysis that excluded papers without full data was performed. RESULTS: The median age at menopause in Europe ranges from 50.1 to 52.8 years, in North America from 50.5 to 51.4 years, in Latin America from 43.8 to 53 years, and in Asia from 42.1 to 49.5 years. The frequency of vasomotor symptoms varies widely depending on the geographical region, selection of criteria, and method of symptom identification. The prevalence of such symptoms ranges from 74% of women in Europe, 36-50% in North America, 45-69% in Latin America and 22-63% in Asia, as reported in different, large, epidemiological studies. CONCLUSION: There are wide geographical differences in the prevalence of menopausal symptomatology and some differences in the age of onset of menopause. Both in Asia and Latin America, women of poorer socioeconomic status have significantly earlier onset of menopause. Within a geographical region, there are ethnic differences in menopause symptoms. Given differences in study methodologies, firm conclusions are not possible. However, regional differences in age at menopause and in climacteric symptoms are important to acknowledge and lay the foundation for an informed approach to the management of menopause and an understanding of its impact on women's health in the different regions of the world.

Preadmission use of glucocorticoids and risk of cardiovascular events in patients with ischemic stroke.

Essentials The risk of thrombosis among ischemic stroke patients using glucocorticoids is unknown. We examined the risk of thrombosis in 98 487 ischemic stroke patients, by glucocorticoid use. Myocardial infarction and venous thromboembolism risk was increased in glucocorticoid users. Hemorrhagic stroke risk was lower and recurrent ischemic stroke the same in glucocorticoid users. SUMMARY: Background Glucocorticoid users have a high mortality rate following stroke, but the underlying clinical pathways are poorly understood. Objectives To examine the risk of cardiovascular events among ischemic stroke patients using glucocorticoids. Methods We conducted a nationwide population-based cohort study by using medical registries in Denmark. We identified all patients hospitalized with a first-time ischemic stroke (2004-2013). We categorized glucocorticoid use into current use (last prescription redemption ≤ 90 days before admission), former use, and non-use. With non-users as reference, we studied the risks of recurrent ischemic stroke, hemorrhagic stroke, myocardial infarction and venous thromboembolism associated with glucocorticoid use. Comorbidity and comedication-adjusted 1-year hazard ratios (aHRs) with 95% confidence intervals (CIs) were computed on the basis of Cox regression analysis. Results We identified 98 487 patients with a first-time (index) ischemic stroke. After the index stroke, the 1-year cumulative incidence of recurrent ischemic stroke was 16.4% among current glucocorticoid users, whereas risks were lower for hemorrhagic stroke (0.46%), myocardial infarction (1.35%), and venous thromboembolism (0.98%). Among current glucocorticoid users, aHRs were increased for myocardial infarction (1.32, 95% CI 0.98-1.76) and venous thromboembolism (1.39, 95% CI 0.99-1.94), whereas the risk of hemorrhagic stroke was reduced (aHR 0.60, 95% CI 0.38-0.93). There was no association with recurrent ischemic stroke (aHR 1.01, 95% CI 0.94-1.09). Conclusions During the first year after ischemic stroke, current glucocorticoid use was associated with moderately increased risks of myocardial infarction and venous thromboembolism, and a lower risk of hemorrhagic stroke, whereas the risk of recurrent ischemic stroke was not affected.

Comorbidity and the increased mortality after hospitalization for stroke: a population-based cohort study.

Essentials Comorbidity is prevalent in the stroke population and affects post-stroke survival. A stroke patient cohort (n = 201 691) and a general population cohort were followed for survival. Cancer and advanced renal/liver disease substantially increased one-year stroke mortality. Tailoring stroke interventions according to comorbidity may reduce excess mortality. SUMMARY: Background Comorbidity is prevalent among stroke patients, affecting post-stroke survival. It remains unknown whether comorbidity impacts post-stroke mortality beyond the combined individual effects of stroke and comorbidity. Methods Using nationwide Danish databases, we performed a cohort study of 201 691 patients ≥ 18 years old with incident ischemic stroke, intracerebral or subarachnoid hemorrhage, or unspecified stroke during 1995-2012, and 992 942 adults from the general population, matched to stroke patients by birth year, sex and individual comorbidities in the Charlson Comorbidity Index. During up to 5 years of follow-up, we computed standardized mortality rates (SMRs) to assess interaction contrasts as a measure of excess mortality not explained by the additive effects of stroke and comorbidity acting alone. Results Five-year post-stroke mortality was 48%, corresponding to an SMR of 187 deaths per 1000 person-years. During the 30-day peak post-stroke mortality (SMR, 180 per 1000 person-months), interaction with comorbidity represented 23%, 34% and 51% of post-stroke mortality rates among patients with low (score = 1), moderate (score = 2-3) and high (score = 4+) comorbidity based on Charlson Comorbidity Index scores. The interaction accounted for 5% to 32% of subsequent 31-365-day post-stroke mortality rates, depending on comorbidity level. The interaction contrasts were most notable among comorbid patients with cancer, particularly with hematological or metastatic disease, followed by patients with moderate-to-severe liver or renal disease. Conclusion Comorbidity, notably cancer and advanced renal or liver disease, increased 1-year mortality after stroke beyond the combined effects expected from either disease acting alone.

Development of a pathway of care for venous leg ulcer management.

During the implementation of a leg ulcer care pathway, it became apparent that training on this subject was often inaccessible and cursory. Additional education was provided, which included a competency assessment of all participants.

A re-appraisal of the normal cut-off assignment for anticardiolipin IgM tests.

BACKGROUND: Recent reports show an apparent large number of individuals with low to moderate titers of anticardiolipin antibodies (ACA), particularly of the IgM isotype with no clinical signs of antiphospholipid syndrome (APS). The significance of these results is unknown. This study examined the prevalence of low positive titers of IgM ACA antibodies in a large number (n = 982) of normal blood donors (Group 1) and in a group of 159 individuals > 60 years of age (Group 2). The effect of re-defining the currently used cut-off values for the IgM ACA tests was also examined. METHODS: IgM ACA antibodies were tested in three ELISA assays: the Bindazyme Anti-IgM Cardiolipin EIA kit (assay A), an 'in-house' ACA test (assay B), and the APhL ELISA kit (assay C). RESULTS: THE normal range cut-offs were re-calculated using the 95th percentile of the data for Group 1 (12.4 MPL U mL(-1) for assay A, 5.4 MPL U mL(-1) for assay B and 9.5 MPL U mL(-1) for assay C) and Group 2 (9.9 MPL U mL(-1) for assay A, 5.5 MPL U mL(-1) for assay B and 13.2 MPL U mL(-1) for assay C). These values were not significantly different from the current cut-off values for each assay. The prevalence of low positive results in Group 1 relative to the re-defined cut-off for that group were: 1.0%, 1.1% and 0.9% in assay A, B and C; and in Group 2: 0.6%, 0.6% and 0.6%, respectively. An indeterminate zone (between the 95th and 99th percentile) was then established for the two groups. The prevalence in Group 1 was 3.8%, 3.9% and 3.9% for assays A, B and C, respectively, and for Group 2: 4.4% in all three assays. CONCLUSIONS: The data confirm that the current cut-off point for each of the three assays is correct. We suggest based on this study that the low positive range is re-assigned 'indeterminate' and recommend that samples falling in this category should be retested to confirm positivity at a later date.

Estrogen-containing hormone therapy and Alzheimer's disease risk: understanding discrepant inferences from observational and experimental research.

Estrogen has the potential to influence brain processes implicated in Alzheimer's disease pathogenesis. With the loss of ovarian estrogen production after menopause, estrogen-containing hormone therapy might be expected to influence the risk of Alzheimer's disease. Observational data link use of hormone therapy to reductions in Alzheimer risk, but experimental evidence from the Women's Health Initiative Memory Study trial demonstrates that oral estrogen, with or without a progestin, increases the incidence of dementia for postmenopausal women age 65 years or older. Mechanisms of harm in this setting are unknown. Bias and unrecognized confounding in observational research are leading candidates for discrepant results between observational studies and the Women's Health Initiative Memory Study trial. Studies are also distinguished by differences in outcome measures, hormone therapy formulations, prevalence of menopausal symptoms among study participants, and participant age. Finally, Women's Health Initiative Memory Study findings may not generalize to estrogen use by relatively young women during the menopausal transition or early postmenopause, a class of women who were ineligible for the Women's Health Initiative Memory Study trial. In observational studies, hormone therapy exposure often included use by younger women for menopausal vasomotor symptoms. Although there is no clinical trial evidence that hormone therapy at any age protects against Alzheimer's disease, it remains to be determined whether the age at which hormone exposure occurs or the timing of hormone therapy initiation in relation to the menopause (the critical window hypothesis) modifies treatment outcomes on dementia risk.

Geographic patterns for pleural mesothelioma deaths in the United States, 1968-81.

Deaths and death rates for mesothelioma of the pleura are presented by age, sex, and geographic area for the United States for the years 1968-81. Death rates increased with age and in every age group were roughly three times higher for males than for females. Over the period 1968-81, death rates increased for males aged 65 years or more, whereas death rates in other age-sex groupings remained fairly constant or declined slightly. It is known that asbestos is highly related to mesothelioma, and the increase in death rates among older males could be due to asbestos. Conversely, the fact that death rates in younger males and in females have not been increasing suggests some kind of background level not strongly related to the use of asbestos. When the geographic distribution of death rates was examined by state, there was considerable geographic variation with some clustering. High death rates for males appeared for the Northeastern States and along the Pacific Coast, and for Illinois, Florida, Wyoming, and Colorado. Females shared this geographic pattern to some extent. When death rates were examined by county, a relationship was seen between pleural mesothelioma deaths among males and the presence of asbestos products plants and shipbuilding facilities. Excessive death rates in some counties and states did not appear to be related to asbestos exposure. Although the similarity in geographic patterns of mortality for males and females suggests a common etiology, the trends in mortality suggest different etiologies. There may be important causes of pleural mesothelioma yet to be identified.

Effect of tetrahydrouridine on the clinical pharmacology of 1-beta-D-arabinofuranosylcytosine when both drugs are coinfused over three hours.

When 1-beta-D-arabinofuranosylcytosine (ara-C), 25 mg/m2, is infused over 3 h together with tetrahydrouridine (THU) at 10 to 350 mg/m2 to heavily pretreated patients with solid tumors, Michaelis-Menten type kinetic values are observed with leveling off of delta area under the curve, delta ara-C levels at 3 h, and delta total body clearance after 150 mg/m2 of THU. When the ara-C dose was increased to 50, 75, and 100 mg/m2 coinfusion of 250 or 350 mg/m2 of THU significantly increased plasma ara-C at peak and area under the curve. In contrast, total body clearance and volume of distribution decreased significantly. At 100 mg/m2 of ara-C coinfused with high doses of THU, i.e., at 350 mg/m2, the pharmacokinetics of plasma ara-C was changed from a biphasic decay of plasma ara-C at peaks (control) to a curve similar or identical to a monophasic curve, indicating that THU not only inhibits deamination but also changes the distribution of ara-C. This combination provides plasma ara-C levels (greater than or equal to 10 microM) comparable to high dose ara-C at 1 g/m2. Such plasma ara-C levels are considered to be sufficient for saturation of the kinases catalyzing the production of 1-beta-D-arabinofuranosylcytosine 5'-triphosphate. This reduced ara-C dose necessary to achieve saturation of kinases also reduces plasma 1-beta-D-arabinofuranosyluracil levels substantially. Toxicity of this combination was predominantly confined to bone marrow and gastrointestinal toxicity.

PO-06 - Cancer and the risk of venous thromboembolism in stroke patients.

INTRODUCTION: The impact of comorbidity and in particular cancer on the risk of venous thromboembolism (VTE) after stroke is poorly understood. AIM: We aimed to determine the impact of comorbidity, in particular cancer, on the risk of venous thromboembolism in stroke patients as the excess VTE rates not explained by stroke and comorbidity alone. MATERIALS AND METHODS: We used Danish national databases to conduct a cohort study including 110,833 patients diagnosed with an incident stroke (72% ischemic) between 1995 and 2012. A comparison cohort of 545,960 members of the general population was matched to the stroke patients by date of diagnosis, year of birth, sex, and specific comorbidities using the Charlson Comorbidity Index and other VTE risk factors. We computed VTE cumulative risks, rates and rate ratios, as well as the interaction with comorbidity (as the excess VTE rates not explained by stroke and comorbidity alone) during five years of follow-up. RESULTS: Five-year VTE risks were 2.16% and 1.85% in the stroke and general population comparison cohorts, respectively. Three-month VTE rate ratios peaked at a 6-fold increase (95% confidence interval: 4.9;6.2) in stroke patients and remained increased by 52%-20% relative to the general population at subsequent follow-up. 20% to 38% of the three-month VTE rates in the stroke cohort were attributable to the interaction between stroke and comorbidity in patients with moderate (2-3) to high (≥4) Charlson Comorbidity Index scores. Non-metastatic and metastatic solid tumors accounted for most of the observed interaction with stroke, representing 44% and 60% of their attributable three-month VTE rates. No interaction between comorbidity and stroke was observed during subsequent follow-up to 5 years. CONCLUSIONS: Cancer increased the risk of VTE within three months after the stroke.

In vivo evaluation of brain iron in Alzheimer disease using magnetic resonance imaging.

BACKGROUND: The basal ganglia contain the highest levels of iron in the brain, and postmortem studies indicate a disruption of iron metabolism in the basal ganglia of patients with Alzheimer disease (AD). Iron can catalyze free radical reactions and may contribute to oxidative damage observed in AD brains. Treatments aimed at reducing oxidative damage have offered novel ways to delay the rate of progression and could possibly defer the onset of AD. Brain iron levels were quantified in vivo using a new magnetic resonance imaging method. METHODS: Thirty-one patients with AD and 68 control subjects participated in this study. A magnetic resonance imaging method was employed that quantifies the iron content of ferritin molecules (ferritin iron) with specificity through the combined use of high and low field-strength magnetic resonance imaging instruments. Three basal ganglia structures (caudate, putamen, and globus pallidus) and one comparison region (frontal lobe white matter) were evaluated. RESULTS: Basal ganglia ferritin iron levels were significantly increased in the caudate (P = .007; effect size, 0.69) and putamen (P = .008; effect size, 0.67) of AD subjects, with a trend toward an increase in the globus pallidus (P = .13). The increased basal ganglia ferritin iron levels were not a generalized phenomenon; white matter ferritin iron levels were unchanged in patients with AD (P = .50). CONCLUSIONS: The data replicate and extend prior results and suggest that basal ganglia ferritin iron levels are increased in AD. Prospective studies are needed to evaluate whether premorbid iron levels are increased in individuals who develop AD.