Improved doppler detection of proximal left anterior descending coronary artery stenosis after intravenous injection of a lung-crossing contrast agent: A transesophageal doppler echocardiographic study

none4noneCarlo Caiati;Pierluigi Aragona;Sabino Iliceto;Paolo RizzonCarlo, Caiati; Pierluigi, Aragona; Iliceto, Sabino; Paolo, Rizzo

A controlled trial of natural cycle versus microdose gonadotropin-releasing hormone analog flare cycles in poor responders undergoing in vitro fertilization

Objective To determine the efficacy of natural-cycle IVF compared with controlled ovarian hyperstimulation in poor responders. Design Randomized, controlled study. Setting Private center for assisted reproduction. Patient(s) One hundred twenty-nine women who were poor responders in a previous IVF cycle. Intervention(s) Fifty-nine women underwent 114 attempts of natural-cycle IVF, and 70 women underwent 101 attempts of IVF with controlled ovarian hyperstimulation with microdose GnRH analog flare. Main outcome measure(s) Number of oocytes retrieved, pregnancy rate (PR) per cycle, PR per transfer, and implantation rate. Result(s) The poor responders treated with natural-cycle IVF and those treated with micro-GnRH analog flare showed similar PRs per cycle and per transfer. The women treated with natural-cycle IVF showed a statistically significant higher implantation rate (14.9%) compared with controls (5.5%). When subdivided into three groups according to age (≤35 years, ≥36-39 years, ≥40 years), younger patients had a better PR than the other two groups. Conclusion(s) In poor responders, natural-cycle IVF is at least as effective as controlled ovarian hyperstimulation, especially in younger patients, with a better implantation rate. © 2004 by American Society for Reproductive Medicine

Bioinformatics filtering algorithm.

<p>Shown are bioinformatics analysis tools used and individual and mean variant numbers at each step of filtering with resulting decrease in variant numbers at each decision step.</p

Resultant variants and dbNSFP scores after bioinformatic filtering in AD-FDC1.

<p>Shown are the six genes containing exome-detected variants present in all three subjects tested. The Genebank NM number, chromosome and nucleotide position are shown along with the predicted consequence of each variant. Only the TNNT2 variant segregates with the disease phenotype in AD-FDC1. SIFT, Polyphen2, LRT, and MutationTaster scores derived from dbNSFP are presented. SIFT scores less than 0.05 are predicted to be damaging, otherwise they are predicted to be tolerated. Polyphen2_HDIV_scores range from 0 to 1. Scores in the range of 0.957 to 1 are predicted to be possibly damaging and those in the range of 0.453 to 0.956 are predicted to be benign. Polyphen2_HVAR_scores range from 0 to 1. Scores in the range of 0.909 to1 are predicted to be possibly damaging and scores in the range of 0.447 to 0.908 are predicted to be benign. Lower LRT p-values correspond to predictions that are more damaging. A MutationTaster value close to 1 indicates a high ‘security’ of the prediction.</p

Pedigrees of families (A) AD-FDC1 and (B) AD-FDC27.

<p>The family structures of both TNNT2 mutation families are shown. The proband is indicated by an arrow. Males and females are depicted as squares and circles, respectively. Affected individuals are identified by shading. Presence or absence of the Arg173Trp variant confirmed by Sanger sequencing is indicated by plus (‘+’) and minus (‘−’) signs, respectively. Paired numbers beneath individuals represent the numbered haplotypes according to (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078104#pone-0078104-t004" target="_blank">Table 4</a>); double-numbers represent recombinant haplotypes further detailed in the <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0078104#pone.0078104.s003" target="_blank">Table S3</a>. Individuals studied by exome sequencing are indicated by present of black underline beneath haplotype numbering.</p

Hap Map project haplotypes and population frequencies of Utah residents with northern and western European ancestry (CEU).

<p>The TNNT2, Arg173Trp variant (Chr1∶201,332,477) was present on separate haplotype, segregating with haplotypes #2 and #1 in families AD-FDC1 and AD-FDC27, respectively.</p

Visualization of NGS alignment and chromatogram from Sanger sequencing confirming the <i>TNNT2 Arg173Trp</i> variant.

<p>The alignment and Sanger sequencing profiles of the TNNT2 R173W variant are shown. A) C>T variant alignment reads of Arg173Trp variant B) (inset) Chromatogram of C>T variant of Arg173Trp variant from Sanger sequencing; arrow depicts the c.517T C>T (chr1∶201,332,477) position.</p

Venn diagram reflecting variant overlap between and among patients.

<p>A Venn diagram depicts the number of variants after bioinformatics filtering to identify nonsynonymous, nonsense and splice site variants that were located in conserved regions (by ANNOVAR), novel (absent in 1000 Genomes and NHLBI Exome Sequencing Project datasets), and were predicted to be damaging by in silico analyses. The numbers and overlap regions in the Venn diagram show the variants unique to or shared among three individuals (IV:4, IV:7, and IV:14) from family AD-FDC1.</p