Aza-annulation of enaminones with crotonyl chloride - Formal reversal of regioselectivity.

The regiochemistry of aza-annulation of enaminones with alpha,beta-unsaturated acid chlorides bearing hydrogen atoms on the gamma-carbon is reversed when triethylamine is used as mediator. When the reaction was carried out at lower temperatures as 3-acyl beta,gamma-unsaturated compound could be isolated which cyclised to the desired product under thermal or basic conditions. The nature of this intermediate strongly suggests that a vinyl ketene is the active acylating agent. (C) 1997 Elsevier Science Ltd.

Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Using dispersive delay lines and time reversal for low contrast tumour detection

On the basis of the technique of time reversal (TR), through adding dispersive delay lines to each element of a TR mirror, a method for low contrast tumour detection is proposed. When compared with a conventional detection method, the proposed method improves refocusing onto a low dielectric contrast tumour. The method does not require an accurate estimate of the position of the tumour. The theoretical basis for the approach is given and numerical simulated results demonstrate the capability of the proposed method.

A rapid dot-blot assay to assess chimerism following sex-mismatched bone marrow transplantation

Mixed chimerism may occur more frequently than previously thought following allogeneic bone marrow transplantation and may have implications in terms of relapse, graft-versus-host disease and immune reconstitution. DNA analysis using single or multilocus polymorphic probes cannot reliably discriminate between donor and recipient cells below a level of 10%. We used probe pHY2.1, a cloned segment of tandemly repeated DNA (2000 copies) on the long arm of chromosome Y. A dot blot procedure allowed us to immobilize DNA directly from 50 microliter of peripheral blood or bone marrow. Cross-reactivity was eliminated by hybridization at conditions of extreme stringency (65 degrees C, 50% formamide). Mixing experiments detected male DNA at a level of 0.1% after 10 h exposure. Five patients were studied serially post-bone marrow transplantation. One patient showed mixed chimerism for 12 months, one had complete autologous recovery and the remaining three showed complete engraftment. All results were verified by standard karyotyping on bone marrow cells. This technique is a simple, rapid and sensitive assay for chimerism following sex mismatched bone marrow transplantation.

Gendered Violence and International Human Rights: Thinking Non-Discrimination Beyond the Sex Binary

The concept of non-discrimination has been central in the feminist challenge to gendered violence within international human rights law. This article critically explores non-discrimination and the challenge it seeks to pose to gendered violence through the work of Judith Butler. Drawing upon Butler’s critique of heteronormative sex/gender, the article utilises an understanding of gendered violence as effected by the restrictive scripts of sex/gender within heteronormativity to illustrate how the development of non-discrimination within international human rights law renders it ineffective to challenge gendered violence due to its own commitments to binarised and asymmetrical sex/gender. However, the article also seeks to encourage a reworking of non-discrimination beyond the heteronormative sex binary through employing Butler’s concept of cultural translation. Analysis via the lens of cultural translation reveals the fluidity of non-discrimination as a universal concept and offers new possibilities for feminist engagement with universal human rights.

Influence of sex on the survival of patients with esophageal cancer

PURPOSE: The prognostic value of sex for esophageal cancer survival is currently unclear, and growing data suggest that hormonal influences may account for incidence disparities between men and women. Therefore, moving from the hypothesis that hormones could affect the prognosis of patients with esophageal cancer, we investigated the primary hypothesis that sex is associated with survival and the secondary hypotheses that the relationship between sex and survival depends, at least in part, on age, histology, and race/ethnicity.

PATIENTS AND METHODS: By using the SEER databases from 1973 to 2007, we identified 13,603 patients (34%) with metastatic esophageal cancer (MEC) and 26,848 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional hazards model for competing risks were used for analyses.

RESULTS: In the multivariate analysis, women had longer esophageal cancer-specific survival (ECSS) than men in both MEC (hazard ratio [HR], 0.949; 95% CI, 0.905 to 0.995; P = .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P < .001) cohorts. When age and histology were accounted for, there was no difference for ECSS between men and women with adenocarcinoma. In contrast, women younger than age 55 years (HR, 0.896; 95% CI, 0.792 to 1.014; P = .081) and those age 55 years or older (HR, 0.905; 95% CI, 0.862 to 0.950; P < .001) with squamous cell LEC had longer ECSS than men. In the squamous cell MEC cohort, only women younger than age 55 years had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P = .011) than men.

CONCLUSION: Sex is an independent prognostic factor for patients with LEC or MEC. As secondary hypotheses, in comparison with men, women age 55 years or older with squamous cell LEC and women younger than age 55 years with squamous cell MEC have a significantly better outcome. These last two findings need further validation.

MRZ-99030 – a novel modulator of Aβ aggregation: II – reversal of Aβ oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice.

β-amyloid1-42 (Aβ1-42) is a major endogenous pathogen underlying the aetiology of Alzheimer's disease (AD). Recent evidence indicates that soluble Aβ oligomers, rather than plaques, are the major cause of synaptic dysfunction and neurodegeneration. Small molecules that suppress Aβ aggregation, reduce oligomer stability or promote off-pathway non-toxic oligomerization represent a promising alternative strategy for neuroprotection in AD. MRZ-99030 was recently identified as a dipeptide that modulates Aβ1-42 aggregation by triggering a non-amyloidogenic aggregation pathway, thereby reducing the amount of intermediate toxic soluble oligomeric Aβ species. The present study evaluated the relevance of these promising results with MRZ-99030 under pathophysiological conditions i.e. against the synaptotoxic effects of Aβ oligomers on hippocampal long term potentiation (LTP) and two different memory tasks. Aβ1-42 interferes with the glutamatergic system and with neuronal Ca2+ signalling and abolishes the induction of LTP. Here we demonstrate that MRZ-99030 (100–500 nM) at a 10:1 stoichiometric excess to Aβ clearly reversed the synaptotoxic effects of Aβ1-42 oligomers on CA1-LTP in murine hippocampal slices. Co-application of MRZ-99030 also prevented the two-fold increase in resting Ca2+ levels in pyramidal neuron dendrites and spines triggered by Aβ1-42 oligomers. In anaesthetized rats, pre-administration of MRZ-99030 (50 mg/kg s.c.) protected against deficits in hippocampal LTP following i.c.v. injection of oligomeric Aβ1-42. Furthermore, similar treatment significantly ameliorated cognitive deficits in an object recognition task and under an alternating lever cyclic ratio schedule after the i.c.v. application of Aβ1-42 and 7PA2 conditioned medium, respectively. Altogether, these results demonstrate the potential therapeutic benefit of MRZ-99030 in AD.

Biometric gonioscopy and the effects of age, race, and sex on the anterior chamber angle.

AIM:

To utilise a novel method for making measurements in the anterior chamber in order to compare the anterior chamber angles of people of European, African, and east Asian descent aged 40 years and over.

METHODS:

A cross sectional study on 15 people of each sex from each decade from the 40s to the 70s, from each of three racial groups-black, white, and Chinese Singaporeans. Biometric gonioscopy (BG) utilises a slit lamp mounted reticule to make measurements from the apparent iris insertion to Schwalbe's line through a Goldmann one mirror goniolens. The main outcome measures were BG measurements of the anterior chamber angle as detailed above.

RESULTS:

There was no significant difference in angle measurement between black, white, and Chinese races in this study. However, at younger ages people of Chinese race appeared to have deeper angles than white or black people, whereas the angles of older Chinese were significantly narrower (p = 0.004 for the difference in slope of BG by age between Chinese and both black and white people).

CONCLUSION:

The failure to detect a difference in angle measurements between these groups was surprising, given the much higher prevalence of angle closure among Chinese. It appears that the overall apparent similarity of BG means between Chinese and Western populations may mask very different trends with age. The apparently more rapid decline in angle width measurements with age among Chinese may be due to the higher prevalence of cataract or "creeping angle closure." However, longitudinal inferences from cross sectional data are problematic, and this may represent a cohort phenomenon caused by the increasing prevalence of myopia in the younger Singaporean population.

Reversal in gender valuations of cataract surgery after the implementation of free screening and low-priced high-quality surgery in a rural population of southern China.

PURPOSE: To assess the impact of community outreach and the availability of low-cost surgeries [500 Renminbi (RMB) or 65 United States dollars (US$) per surgery] on the willingness to pay for cataract surgery among male and female rural-dwelling Chinese.METHODS: Cross-sectional willingness-to-pay surveys were conducted at the initiation of a cataract outreach programme in June 2001 and then again in July 2006. Respondents underwent visual acuity testing and provided socio-demographic data.RESULTS: In 2001 and 2006, 325 and 303 subjects, respectively, were interviewed. On average the 2006 sample subjects were of similar age, more likely to be female (p < 0.01), illiterate (p < 0.01), and less likely to come from a household with annual income of less than US$789 (62% vs. 87%, p < 0.01). Familiarity with cataract surgery increased from 21.2% to 44.4% over the 5 years for male subjects (p < 0.01) and 15.8%-44.4% among females (p < 0.01). The proportion of respondents willing to pay at least 500 RMB for surgery increased from 67% to 88% (p < 0.01) among male subjects and from 50% to 91% (p < 0.01) among females.CONCLUSIONS: Five years of access to free cataract testing and low-cost surgery programmes appears to have improved the familiarity with cataract surgery and increased the willingness to pay at least 500 RMB (US$65) for it in this rural population. Elderly women are now as likely as men to be willing to pay at least 500 RMB, reversing gender differences present 5 years ago.

Spatial variation in adult sex ratio across multiple scales in the invasive golden apple snail, Pomacea canaliculata

Adult sex ratio (ASR) has critical effects on behavior and life history and has implications for population demography, including the invasiveness of introduced species. ASR exhibits immense variation in nature, yet the scale dependence of this variation is rarely analyzed. In this study, using the generalized multilevel models, we investigated the variation in ASR across multiple nested spatial scales and analyzed the underlying causes for an invasive species, the golden apple snail Pomacea canaliculata. We partitioned the variance in ASR to describe the variations at different scales and then included the explanatory variables at the individual and group levels to analyze the potential causes driving the variation in ASR. We firstly determined there is a significant female-biased ASR for this species when accounting for the spatial and temporal autocorrelations of sampling. We found that, counter to nearly equal distributed variation at plot, habitat and region levels, ASR showed little variation at the town level. Temperature and precipitation at the region level were significantly positively associated with ASR, whereas the individual weight, the density characteristic, and sampling time were not significant factors influencing ASR. Our study suggests that offspring sex ratio of this species may shape the general pattern of ASR in the population level while the environmental variables at the region level translate the unbiased offspring sex ratio to the female-biased ASR. Future research should consider the implications of climate warming on the female-biased ASR of this invasive species and thus on invasion pattern.