Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome

Background The polycystic ovary syndrome is a common cause of infertility. Clomiphene and insulin sensitizers are used alone and in combination to induce ovulation, but it is unknown whether one approach is superior. Methods We randomly assigned 626 infertile women with the polycystic ovary syndrome to receive clomiphene citrate plus placebo, extended-release metformin plus placebo, or a combination of metformin and clomiphene for up to 6 months. Medication was discontinued when pregnancy was confirmed, and subjects were followed until delivery. Results The live-birth rate was 22.5% (47 of 209 subjects) in the clomiphene group, 7.2% (15 of 208) in the metformin group, and 26.8% (56 of 209) in the combinationtherapy group (P\u3c0.001 for metformin vs. both clomiphene and combination therapy; P=0.31 for clomiphene vs. combination therapy). Among pregnancies, the rate of multiple pregnancy was 6.0% in the clomiphene group, 0% in the metformin group, and 3.1% in the combination-therapy group. The rates of first-trimester pregnancy loss did not differ significantly among the groups. However, the conception rate among subjects who ovulated was significantly lower in the metformin group (21.7%) than in either the clomiphene group (39.5%, P=0.002) or the combinationtherapy group (46.0%, P\u3c0.001). With the exception of pregnancy complications, adverse-event rates were similar in all groups, though gastrointestinal side effects were more frequent, and vasomotor and ovulatory symptoms less frequent, in the metformin group than in the clomiphene group. Conclusions Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication. (ClinicalTrials.gov number, NCT00068861.

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour

Compensation and advancement of women in academic medicine: is there equity

BACKGROUND: Women have been entering academic medicine in numbers at least equal to their male colleagues for several decades. Most studies have found that women do not advance in academic rank as fast as men and that their salaries are not as great. These studies, however, have typically not had the data to examine equity, that is, do women receive similar rewards for similar achievement? OBJECTIVE: To examine equity in promotion and salary for female versus male medical school faculty nationally. DESIGN: Mailed survey questionnaire. SETTING: 24 randomly selected medical schools in the contiguous United States. PARTICIPANTS: 1814 full-time U.S. medical school faculty in 1995-1996, stratified by sex, specialty, and graduation cohort. MEASUREMENTS: Promotion and compensation of academic medical faculty. RESULTS: Among the 1814 faculty respondents (response rate, 60%), female faculty were less likely to be full professors than were men with similar professional roles and achievement. For example, 66% of men but only 47% of women (P \u3c 0.01) with 15 to 19 years of seniority were full professors. Large deficits in rank for senior faculty women were confirmed in logistic models that accounted for a wide range of other professional characteristics and achievements, including total career publications, years of seniority, hours worked per week, department type, minority status, medical versus nonmedical final degree, and school. Similar multivariable modeling also confirmed gender inequity in compensation. Although base salaries of nonphysician faculty are gender comparable, female physician faculty have a noticeable deficit (-11,691 dollars; P = 0.01). Furthermore, both physician and nonphysician women with greater seniority have larger salary deficits (-485 dollars per year of seniority; P = 0.01). Limitations: This is a cross-sectional study of a longitudinal phenomenon. No data are available for faculty who are no longer working full-time in academic medicine, and all data are self-reported. CONCLUSIONS: Female medical school faculty neither advance as rapidly nor are compensated as well as professionally similar male colleagues. Deficits for female physicians are greater than those for nonphysician female faculty, and for both physicians and nonphysicians, women\u27s deficits are greater for faculty with more seniority

Lo-Fi prototyping to design interactive-tabletop applications for children

Interactive tabletops are an exiting new platform for supporting children's collaboration. With design guidelines and standardized interaction principles still immature, there is a considerable need for iterative prototyping to define the task and interface. Lo-fi prototypes-using cardboard, paper, etc.-are easy to develop, flexible to adjust during design sessions, and intuitive for users to manipulate. Using them can be a valuable step in designing tabletop applications. In this paper, we detail the design process of two tabletop applications, concentrating on the role of lo-fi prototyping. TransTime is a pattern game for 5-6 year olds to engage how time progresses. OurSpace is a design tool for 7-9 year olds to arrange desks and assign seats for students in their classroom. By comparing the experiences, we arrive at a better understanding of the benefits, challenges, and limits of using lo-fi prototypes to design interactive-tabletop applications for children. Copyright 2010 ACM

Hyperoxic Exposure Caused Lung Lipid Compositional Changes in Neonatal Mice

Treatments with supplemental oxygen in premature infants can impair lung development, leading to bronchopulmonary dysplasia (BPD). Although a stage-specific alteration of lung lipidome occurs during postnatal lung development, whether neonatal hyperoxia, a known mediator of BPD in rodent models, changes lipid profiles in mouse lungs is still to be elucidated. To answer this question, newborn mice were exposed to hyperoxia for 3 days and allowed to recover in normoxia until postnatal day (pnd) 7 and pnd14, time-points spanning the peak stage of alveologenesis. A total of 2263 lung lipid species were detected by liquid chromatography&ndash;mass spectrometry, covering 5 lipid categories and 18 lipid subclasses. The most commonly identified lipid species were glycerophospholipids, followed by sphingolipids and glycerolipids. In normoxic conditions, certain glycerophospholipid and glycerolipid species augmented at pnd14 compared to pnd7. At pnd7, hyperoxia generally increased glycerophospholipid, sphingolipid, and glycerolipid species. Hyperoxia increased NADPH, acetyl CoA, and citrate acid but reduced carnitine and acyl carnitine. Hyperoxia increased oxidized glutathione but reduced catalase. These changes were not apparent at pnd14. Hyperoxia reduced docosahexaenoic acid and arachidonic acid at pnd14 but not at pnd7. Altogether, the lung lipidome changes throughout alveolarization. Neonatal hyperoxia alters the lung lipidome, which may contribute to alveolar simplification and dysregulated vascular development