Diagnostic and treatment characteristics of polycystic ovary syndrome: descriptive measurements of patient perception and awareness from 657 confidential self-reports

BACKGROUND: This investigation was undertaken to describe patient perception and awareness of the polycystic ovary syndrome (PCOS), the most common cause of anovulation/oligoovulation among women of reproductive age. METHODS: Fifteen parameters were evaluated by a computer-based research instrument accessed by a large, unscreened population. Incomplete questionnaires were not entered, and responses were electronically tabulated to block duplicate submissions. RESULTS: From 657 participants, the majority (63%) were between 26–34 years old; mean BMI was 30.4 kg/m(2). 343 of 657 had at least one pregnancy and 61% of the study group had taken fertility medicine (any type) at least once. Physicians were the most common provider of PCOS information for all study participants, irrespective of age. Patient emotions associated with the diagnosis of PCOS included "frustration" (67%), "anxiety" (16%), "sadness" (10%), and "indifference" (2%). Self-reported patient aptitude regarding PCOS was scored as high or "very aware" in >60% of women. Respondents were also asked: "If your PCOS could be safely and effectively helped by something else besides fertility drugs or birth control pills, would that interest you?" Interest in alternative PCOS treatments was expressed by 99% of the sample (n = 648). CONCLUSIONS: In our study population, most women associated negative emotions with PCOS although the self-reported knowledge level for the disorder was high. While these women regarded their obstetrician-gynecologist as integral to their PCOS education, traditional PCOS therapies based on oral contraceptives or ovulation induction agents were regarded as unsatisfactory by most women

Ocean temperature and salinity components of the Madden-Julian oscillation observed by Argo floats

New diagnostics of the Madden-Julian Oscillation (MJO) cycle in ocean temperature and, for the first time, salinity are presented. The MJO composites are based on 4 years of gridded Argo float data from 2003 to 2006, and extend from the surface to 1,400 m depth in the tropical Indian and Pacific Oceans. The MJO surface salinity anomalies are consistent with precipitation minus evaporation fluxes in the Indian Ocean, and with anomalous zonal advection in the Pacific. The Argo sea surface temperature and thermocline depth anomalies are consistent with previous studies using other data sets. The near-surface density changes due to salinity are comparable to, and partially offset, those due to temperature, emphasising the importance of including salinity as well as temperature changes in mixed-layer modelling of tropical intraseasonal processes. The MJO-forced equatorial Kelvin wave that propagates along the thermocline in the Pacific extends down into the deep ocean, to at least 1,400 m. Coherent, statistically significant, MJO temperature and salinity anomalies are also present in the deep Indian Ocean

Light hadron, Charmonium(-like) and Bottomonium(-like) states

Hadron physics represents the study of strongly interacting matter in all its manifestations and the understanding of its properties and interactions. The interest on this field has been revitalized by the discovery of new light hadrons, charmonium- and bottomonium-like states. I review the most recent experimental results from different experiments.Comment: Presented at Lepton-Photon 2011, Mumbai, India; 21 pages, 18 figures; add more references; some correctio

A High-Density Genome-Wide Association Screen of Sporadic ALS in US Veterans

Following reports of an increased incidence of amyotrophic lateral sclerosis (ALS) in U.S. veterans, we have conducted a high-density genome-wide association study (GWAS) of ALS outcome and survival time in a sample of U.S. veterans. We tested ∼1.3 million single nucleotide polymorphisms (SNPs) for association with ALS outcome in 442 incident Caucasian veteran cases diagnosed with definite or probable ALS and 348 Caucasian veteran controls. To increase power, we also included genotypes from 5909 publicly-available non-veteran controls in the analysis. In the survival analysis, we tested for association between SNPs and post-diagnosis survival time in 639 Caucasian veteran cases with definite or probable ALS. After this discovery phase, we performed follow-up genotyping of 299 SNPs in an independent replication sample of Caucasian veterans and non-veterans (ALS outcome: 183 cases and 961 controls; survival: 118 cases). Although no SNPs reached genome-wide significance in the discovery phase for either phenotype, three SNPs were statistically significant in the replication analysis of ALS outcome: rs6080539 (177 kb from PCSK2), rs7000234 (4 kb from ZNF704), and rs3113494 (13 kb from LOC100506746). Two SNPs located in genes that were implicated by previous GWA studies of ALS were marginally significant in the pooled analysis of discovery and replication samples: rs17174381 in DPP6 (p = 4.4×10−4) and rs6985069 near ELP3 (p = 4.8×10−4). Our results underscore the difficulty of identifying and convincingly replicating genetic associations with a rare and genetically heterogeneous disorder such as ALS, and suggest that common SNPs are unlikely to account for a substantial proportion of patients affected by this devastating disorder

Genome-wide association reveals three SNPs associated with sporadic amyotrophic lateral sclerosis through a two-locus analysis

<p>Abstract</p> <p>Background</p> <p>Amyotrophic lateral sclerosis (ALS) is a fatal, degenerative neuromuscular disease characterized by a progressive loss of voluntary motor activity. About 95% of ALS patients are in "sporadic form"-meaning their disease is not associated with a family history of the disease. To date, the genetic factors of the sporadic form of ALS are poorly understood.</p> <p>Methods</p> <p>We proposed a two-stage approach based on seventeen biological plausible models to search for two-locus combinations that have significant joint effects to the disease in a genome-wide association study (GWAS). We used a two-stage strategy to reduce the computational burden associated with performing an exhaustive two-locus search across the genome. In the first stage, all SNPs were screened using a single-marker test. In the second stage, all pairs made from the 1000 SNPs with the lowest p-values from the first stage were evaluated under each of the 17 two-locus models.</p> <p>Results</p> <p>we performed the two-stage approach on a GWAS data set of sporadic ALS from the SNP Database at the NINDS Human Genetics Resource Center DNA and Cell Line Repository <url>http://ccr.coriell.org/ninds/</url>. Our two-locus analysis showed that two two-locus combinations--rs4363506 (SNP1) and rs3733242 (SNP2), and rs4363506 and rs16984239 (SNP3) -- were significantly associated with sporadic ALS. After adjusting for multiple tests and multiple models, the combination of SNP1 and SNP2 had a p-value of 0.032 under the Dom∩Dom epistatic model; SNP1 and SNP3 had a p-value of 0.042 under the Dom × Dom multiplicative model.</p> <p>Conclusion</p> <p>The proposed two-stage analytical method can be used to search for joint effects of genes in GWAS. The two-stage strategy decreased the computational time and the multiple testing burdens associated with GWAS. We have also observed that the loci identified by our two-stage strategy can not be detected by single-locus tests.</p

EGFR and EGFRvIII Expression in Primary Breast Cancer and Cell Lines

EGFRvIII is a constitutively activated truncated variant of the epidermal growth factor receptor (EGFR) which has been shown to increase tumorgenicity. There are conflicting reports on the extent of EGFRvIII expression in tissues which may in part stem from the use of different assay methodologies. We investigated the expression of both EGFRvIII and wild-type EGFR (EGFRwt) in cell lines and primary breast cancers. First, we used a RT-PCR assay that can simultaneously measure EGFRwt and EGFRvIII mRNA to screen 55 tumor cell lines. We show that except for EGFRvIII transfected cells, only EGFRwt was detected. We then validated a real-time PCR assay and used this to screen 170 formalin fixed paraffin-embedded primary breast cancers for evidence of EGFRwt and EGFRvIII expression. No samples were positive for EGFRvIII expression except for control transfectants and glioblastomas. In contrast, EGFRwt was expressed at varying levels in the majority of samples tested. We conclude that the expression of EGFRvIII is extremely rare in breast cancer and therefore it does not contribute to the malignant phenotype.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44224/1/10549_2004_Article_5274918.pd

Experimental Oral Transmission of Chronic Wasting Disease to Reindeer (Rangifer tarandus tarandus)

Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, remains prevalent in North American elk, white-tailed deer and mule deer. A natural case of CWD in reindeer (Rangifer tarandus tarandus) has not been reported despite potential habitat overlap with CWD-infected deer or elk herds. This study investigates the experimental transmission of CWD from elk or white-tailed deer to reindeer by the oral route of inoculation. Ante-mortem testing of the three reindeer exposed to CWD from white-tailed deer identified the accumulation of pathological PrP (PrPCWD) in the recto-anal mucosa associated lymphoid tissue (RAMALT) of two reindeer at 13.4 months post-inoculation. Terminal CWD occurred in the two RAMALT-positive reindeer at 18.5 and 20 months post-inoculation while one other reindeer in the white-tailed deer CWD inoculum group and none of the 3 reindeer exposed to elk CWD developed disease. Tissue distribution analysis of PrPCWD in CWD-affected reindeer revealed widespread deposition in central and peripheral nervous systems, lymphoreticular tissues, the gastrointestinal tract, neuroendocrine tissues and cardiac muscle. Analysis of prion protein gene (PRNP) sequences in the 6 reindeer identified polymorphisms at residues 2 (V/M), 129 (G/S), 138 (S/N) and 169 (V/M). These findings demonstrate that (i) a sub-population of reindeer are susceptible to CWD by oral inoculation implicating the potential for transmission to other Rangifer species, and (ii) certain reindeer PRNP polymorphisms may be protective against CWD infection

PolyQ Repeat Expansions in ATXN2 Associated with ALS Are CAA Interrupted Repeats

Amyotrophic lateral sclerosis (ALS) is a devastating, rapidly progressive disease leading to paralysis and death. Recently, intermediate length polyglutamine (polyQ) repeats of 27–33 in ATAXIN-2 (ATXN2), encoding the ATXN2 protein, were found to increase risk for ALS. In ATXN2, polyQ expansions of ≥34, which are pure CAG repeat expansions, cause spinocerebellar ataxia type 2. However, similar length expansions that are interrupted with other codons, can present atypically with parkinsonism, suggesting that configuration of the repeat sequence plays an important role in disease manifestation in ATXN2 polyQ expansion diseases. Here we determined whether the expansions in ATXN2 associated with ALS were pure or interrupted CAG repeats, and defined single nucleotide polymorphisms (SNPs) rs695871 and rs695872 in exon 1 of the gene, to assess haplotype association. We found that the expanded repeat alleles of 40 ALS patients and 9 long-repeat length controls were all interrupted, bearing 1–3 CAA codons within the CAG repeat. 21/21 expanded ALS chromosomes with 3CAA interruptions arose from one haplotype (GT), while 18/19 expanded ALS chromosomes with <3CAA interruptions arose from a different haplotype (CC). Moreover, age of disease onset was significantly earlier in patients bearing 3 interruptions vs fewer, and was distinct between haplotypes. These results indicate that CAG repeat expansions in ATXN2 associated with ALS are uniformly interrupted repeats and that the nature of the repeat sequence and haplotype, as well as length of polyQ repeat, may play a role in the neurological effect conferred by expansions in ATXN2