Objective
We assessed whether (1) women with statistical clustering of daily seizure counts (DSCs) or seizure intervals (SIs) also showed clinical clustering, defined separately by ≥2 (≥2‐SC) and ≥3 ...(≥3‐SC) seizures on any single day; and (2) how these classifiers might apply to catamenial epilepsy.
Methods
This is a retrospective case–control analysis of data from 50 women with epilepsy (WWE). We assessed the relationships of the four classifiers to each other and to catamenial versus noncatamenial epilepsy using chi‐squared, correlation, logistic regression, and receiver operating characteristic (ROC) analyses.
Results
≥3‐SC, not ≥2‐SC, was more frequent in WWE who had statistical DSC clustering versus those who did not (21/25 84.0% vs. 11/25 44.0%, p = .007). Logistic regression (p = .006) and ROC (p = .015) identified ≥3‐SC, not ≥2‐SC, as a predictor of statistical DSC clustering, but ≥4‐SC was more accurate. ≥3‐SC correlated with the average daily seizure frequencies (ADSFs) of the subjects (p = .01). ROC optimal sensitivity–specificity cut‐point for ADSF prediction of ≥3‐SC (.372) was 64.6% higher than for ≥2‐SC (.226). SI clustering was more common in WWE who had catamenial versus noncatamenial epilepsy (p = .013). Logistic regression identified statistical SI clustering as the only significant classifier (p = .043). ROC analysis offered only marginal support (p = .056), because specificity was low (42.1%).
Significance
The findings lend statistical support for (1) the utility of clinical ≥3‐SC as a predictor of convulsive status epilepticus, (2) consideration of ADSFs in defining clustering, and (3) ≥4‐SC as a more accurate clinical predictor of statistical DSC clustering. Statistical SI clustering occurred more frequently in women with catamenial than noncatamenial epilepsy (90.3% vs. 57.9%, p = .013). Although sensitivity was high (90.3%, 28/31), specificity was only 42.1% (8/19). Algorithms that test patterns and periodicities of clusters are more applicable.
To assess progesterone treatment of intractable seizures in women with partial epilepsy.
This randomized, double-blind, placebo-controlled, phase III, multicenter, clinical trial compared the ...efficacy and safety of adjunctive cyclic natural progesterone therapy vs placebo treatment of intractable seizures in 294 subjects randomized 2:1 to progesterone or placebo, stratified by catamenial and noncatamenial status. It compared treatments on proportions of ≥50% responders and changes in seizure frequency from 3 baseline to 3 treated menstrual cycles.
There was no significant difference in proportions of responders between progesterone and placebo in the catamenial and noncatamenial strata. Prespecified secondary analysis showed that the level of perimenstrual seizure exacerbation (C1 level) was a significant predictor of responders for progesterone but not placebo. With increasing C1 levels, responders increased from 21% to 57% with progesterone vs 19% to 20% with placebo. Reductions in seizure frequency correlated with increasing C1 levels for progesterone but not placebo, progressing from 26% to 71% for progesterone vs 25% to 26% for placebo. A prespecified clinically important separation between progesterone and placebo responders (37.8% vs 11.1%; p = 0.037) was realized among 21.4% of women who had C1 level ≥3.
There was no difference in the primary outcome of ≥50% responder rates between progesterone vs placebo for catamenial or noncatamenial groups. Post hoc findings suggest that the level of perimenstrual seizure exacerbation is a significant predictor of responder rate with progesterone and that progesterone may provide clinically important benefit for a subset of women with perimenstrually exacerbated seizures.
This study provides Class III evidence that cyclic progesterone is ineffective in women with intractable partial epilepsy. Post hoc analysis identified a subset of women with higher levels of perimenstrual seizure exacerbation that were responsive to treatment.
We used ICP–MS to measure the elemental concentrations and isotopic abundances of Cu and Zn in: nine Ti-rich lunar basalts (10017, 10022, 10024, 10057, 70215, 71055, 74255, 75055, and 75075); ...size-separated samples prepared by sieving of pyroclastic black glass 74001, orange glass 74022, and the lunar soils 15021, 15231, 70181, and 79221; a basalt from the Piton des Neiges volcano, Reunion Island; two samples of Pele’s hairs from the Nyiragongo volcano, Democratic Republic of Congo, and the martian meteorite Zagami.
The isotopic fractionation of zinc in lunar basalts and Zagami is mass dependent relative to a terrestrial standard (JMC 400882B). These and published results imply that lunar, terrestrial, meteoritic, and perhaps martian zinc all come from one or more reservoirs linked by mass-dependent fractionation processes. Relative to terrestrial basalts, Ti-rich lunar basalts are enriched in the heavier isotopes of Cu and Zn: we find for Ti-rich lunar basalts the following ranges and averages ±1
−
σ (‰): δ
65Cu/
63Cu
≡
δ
65Cu, 0.1–1.4, 0.5
±
0.1‰ (
N
=
7); δ
66Zn/
64Zn
≡
δ
66Zn
=
0.2–1.9, 1.2
±
0.2‰ (
N
=
8; 10017 excluded). For two terrestrial samples, we find δ
66Zn
∼
+0.3‰ and δ
65Cu
∼
0‰, which are consistent with published values. The differences between the lunar basalts and terrestrial basalts could reflect minor, planetary-scale vaporization or igneous processes on the Moon.
Data for size separates of the pyroclastic glasses 74001 and 74220 confirm the well-known surface correlation of Cu and Zn, but modeling calculations reveal no sharp differences between either the elemental ratios or the isotopic composition of grain interiors and exteriors. The absence of such differences indicates that the isotopic compositions for bulk samples are dominated by a light-isotope-rich surface component.
Data for size separates of lunar soils also confirm the surface correlation of Cu and Zn, but an enrichment of heavy rather than light isotopes. Averages for bulk lunar soils from this work and the literature are (‰): δ
65Cu, from 1.4 to 4.1, average 3.0
±
0.3 (
N
=
9); δ
66Zn, from 2.2 to 6.4, average 4.0
±
0.3 (
N
=
14). As with the glasses, in all but soil 15231 our data show no strong differences between the isotopic composition of soil sub-samples with small and large grains.
The size of the isotopic fractionation inferred for the surface component in the soils is 3× smaller than predicted by a published model of sputtering primarily by solar particles. At the same time, the observed fractionation is larger than predicted by calculations based on a model of micrometeorite impact heating and hydrodynamic quenching. Because impact heating appears unable to explain the observations, we conclude that sputtering must be important even though samples with very large isotopic fractionation of Cu and Zn have not yet been found.
We determined by ICP-MS the concentrations and isotopic ratios of Fe, Cu, and Zn in the Ti-rich lunar basalt 74275, in the lunar orange glass 74220, and in up to 10 lunar soils, namely, 14163, 15231, ...64501, 66041, 68841, 69941, 70011, 72501, 75081, and 76501. Two analyses of zinc in lunar basalt 74275 give δ
66Zn
=
0.17‰ and 0.75‰, values within the range of those measured in terrestrial basalts; copper in lunar basalt 74275 has δ
65Cu
∼
+1.4‰, which is isotopically heavier than values observed in terrestrial basalts. In the orange glass, we measured δ
56Fe
=
−0.24‰, δ
65Cu
=
−0.42‰, and δ
66Zn
∼
−3.6‰. These values of δ are more negative than those obtained for 74275 and for typical lunar basalts, but for Cu, comparable to those observed in terrestrial sulfides and meteorites. In lunar soils we found 0.11‰
⩽
δ
56Fe
⩽
0.51‰, 2.6‰
⩽
δ
65Cu
⩽
4.5‰, and 2.2‰
⩽
δ
66Zn
⩽
6.4‰. Insofar as we can generalize from a small sample set, S, Fe, Cu, Zn, and Cd show similar trends in isotopic fractionation on the Moon. Lunar basalts have nearly terrestrial isotopic ratios. Relative to the lunar basalt 74275, the pyroclastic glass 74220 is enriched in the lighter isotopes of Fe, Cu, and Zn, and the soils are enriched in the heavier isotopes of Fe, Cu, and Zn. The patterns in the basalts are likely inherited from the source material; the light-isotope enrichments seen in the orange glass originated during lava fountaining or, less probably, during partial condensation of vapor; and the heavy-isotope enrichments in the lunar soils were likely created by a combination of processes that included micrometeorite vaporization and sputtering. In the orange glass, the light-isotope enrichments (relative to lunar basalts) of Zn are larger than those of Cu. If these enrichments reflect accurately the isotopic composition of the gas, they suggest that Cu is more volatile than Zn in the liquid from which the gas derived. A simple model built on the known flux of micrometeorites to the lunar surface and a published estimate that micrometeorites generate 10 times their own mass of vapor, predicts heavy-isotope enrichments comparable to those observed in soils but only if the regolith gardening rate is set at about one twentieth of the generally accepted value of 1
cm/My. This discrepancy may reflect the difference in the time constants for micrometeorite milling and decimeter-scale gardening, or the importance of sputtering.
The purpose of this investigation was to determine whether a family history of alcohol use disorder (AUD) might be a risk factor and possible clinical biomarker for catamenial epilepsy. The ...retrospective case–control data came from 119 women, aged 13–48 years, with intractable seizures. We report the relative risk for positive family history of AUD among women with catamenial epilepsy (Group 1) relative to women with noncatamenial epilepsy (Group 2). The risk ratio (RR) for positive AUD history for Group 1 (n = 59) relative to Group 2 (n = 60) was 3.46 (95% confidence interval = 1.36–8.76, p = .009). The RRs were significant for women who had the (C1) perimenstrual (p = .009) and (C3) entire luteal phase (p = .003) patterns but not the (C2) preovulatory pattern. AUD history had a high specificity of 91.7% (55/60) but relatively low sensitivity of 28.8% (17/59) for the prediction of catamenial epilepsy. The positive predictive value was 77.3% (17/22), whereas the negative predictive value was 56.7% (55/97). AUD history is a highly specific biomarker for catamenial epilepsy but has relatively low sensitivity for its detection. Further investigation may identify additional biomarkers that are more efficient than seizure–menses calendars.
Highlights • Seizure occurrence and numbers vary by the day and phase of the menstrual cycle. • Seizures vary by the ovulatory versus anovulatory status of menstrual cycles. • 3 patterns of ...catamenial epilepsy: perimenstrual, peri-ovulatory, luteal phase. • Reproductive steroids have neuroactive properties that affect neuronal excitability and seizures. • Cyclic progesterone supplement may benefit perimenstrually exacerbated seizures.
The thermal switching behavior of individual in-plane magnetized Fe/W(110) nanoislands is investigated by a combined study of variable-temperature spin-polarized scanning tunneling microscopy and ...Monte Carlo simulations. Even for islands consisting of less than 100 atoms the magnetization reversal takes place via nucleation and propagation. The Arrhenius prefactor is found to strongly depend on the individual island size and shape, and based on the experimental results a simple model is developed to describe the magnetization reversal in terms of metastable states. Complementary Monte Carlo simulations confirm the model and provide new insight into the microscopic processes involved in magnetization reversal of smallest nanomagnets.
To compare sexual function and reproductive hormone levels among men with epilepsy who took various antiepileptic drugs (AEDs), untreated men with epilepsy, and normal controls.
Subjects were 85 men ...with localization-related epilepsy (25 on carbamazepine CBZ, 25 on phenytoin PHT, 25 on lamotrigine LTG, and 10 untreated for at least 6 months no AED) and 25 controls. Sexual function scores (S-scores), hormone levels (bioactive testosterone, estradiol), hormone ratios (bioactive testosterone/bioactive estradiol), and gonadal efficiency (bioactive testosterone/luteinizing hormone) were compared among the five groups.
S-scores, bioactive testosterone levels, bioactive testosterone/bioactive estradiol, and bioactive testosterone/luteinizing hormone were significantly greater in the control and LTG groups than in the CBZ and PHT groups. Sex hormone binding globulin was significantly higher in the CBZ and PHT groups than in all other groups. S-scores were below the control range in 20% of the men with epilepsy, including 32.0% on CBZ, 24% on PHT, 20% on no AEDs, and 4% on LTG (chi2: p = 0.08 for all four groups; chi2: p = 0.02 for the three AED groups). Bioactive testosterone was below the control range in 28.2%, including 48% on CBZ, 28% on PHT, 20% on no AEDs, and 12% on LTG (chi2: p = 0.02). Among men with epilepsy who had low S-scores, 70.6% had bioactive testosterone levels below the control range as compared to 17.6% among men with normal S-scores (chi2: p < 0.0001). Among men with epilepsy who had abnormally low bioactive testosterone, 50.0% had low S-scores; among men with normal bioactive testosterone, 8.2% had low S-scores (chi2: p < 0.0001). Bioactive testosterone decline with age was significantly greater among men with epilepsy than among controls and notably greater in the CBZ and PHT groups than in the LTG and untreated groups.
Sexual function, bioavailable testosterone levels, and gonadal efficiency in men with epilepsy who took lamotrigine were comparable to control and untreated values and significantly greater than with carbamazepine or phenytoin treatment.
Switching the magnetization of a magnetic bit by injection of a spin-polarized current offers the possibility for the development of innovative high-density data storage technologies. We show how ...individual superparamagnetic iron nanoislands with typical sizes of 100 atoms can be addressed and locally switched using a magnetic scanning probe tip, thus demonstrating current-induced magnetization reversal across a vacuum barrier combined with the ultimate resolution of spin-polarized scanning tunneling microscopy. Our technique allows us to separate and quantify three fundamental contributions involved in magnetization switching (i.e., current-induced spin torque, heating the island by the tunneling current, and Oersted field effects), thereby providing an improved understanding of the switching mechanism.
Aim: To evaluate caries prevalence in non-syndromic patients with cleft lip and/or palate (CLP) in comparison with a matched non-CLP population. Methods: A literature search was conducted in order to ...identify articles reporting on the prevalence of caries in CLP versus non-CLP individuals. The related citations function in PubMed and reference lists of retrieved articles were used to expand the search. Only studies with a suitable matched control group were included. From each included study, study and sample characteristics were extracted, as were results. The main outcome was the score given for caries prevalence in each study, using a well-defined index. The data were entered into meta-analysis software and a meta-analysis performed using the random-effects model. Results: From the 592 articles initially identified, 7 were chosen according to preset inclusion and exclusion criteria. All of the studies were cross-sectional in nature, and used the decayed, missing, and filled (DMF/dmf) indices as the final outcomes. The included studies involved a total of 474 CLP patients aged 1.5-29 years. When looking at permanent teeth, data from 5 studies suggest that CLP patients have a higher number of DMF teeth than the controls (mean difference 1.38; p = 0.003). For deciduous teeth, data from 4 studies suggest that CLP patients have a higher number of dmf teeth than the controls (mean difference 1.51; p = 0.03). Conclusion: Non-syndromic patients with CLP tend to have higher caries prevalence, both in the permanent and the deciduous dentition, in comparison with matched non-CLP controls.
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