Optimization of Time- and Code-Division-Multiplexed Readout for Athena X-IFU.

Readout of a large, spacecraft-based array of superconducting transition-edge sensors (TESs) requires careful management of the layout area and power dissipation of the cryogenic-circuit components. We present three optimizations of our time- (TDM) and code-division-multiplexing (CDM) systems for the X-ray Integral Field Unit (X-IFU), a several-thousand-pixel-TES array for the planned Athena-satellite mission. The first optimization is a new readout scheme that is a hybrid of CDM and TDM. This C/TDM architecture balances CDM's noise advantage with TDM's layout compactness. The second is a redesign of a component: the shunt resistor that provides a dc-voltage bias to the TESs. A new layout and a thicker Pd-Au resistive layer combine to reduce this resistor's area by more than a factor of 5. Third, we have studied the power dissipated by the first-stage SQUIDs (superconducting quantum-interference devices) and the readout noise versus the critical current of the first-stage SqUIDs. As a result, the X-IFU TDM and C/TDM SQUIDs will have a specified junction critical current of 5 µA. Based on these design optimizations and TDM experiments described by Durkin, et al. (these proceedings), TDM meets all requirements to be X-IFU's backup-readout option. Hybrid C/TDM is another viable option that could save spacecraft resources.

Demonstration of Athena X-IFU Compatible 40-Row Time-Division-Multiplexed Readout.

Time-division multiplexing (TDM) is the backup readout technology for the X-ray Integral Field Unit (X-IFU), a 3,168-pixel X-ray transition-edge sensor (TES) array that will provide imaging spectroscopy for ESA's Athena satellite mission. X-0IFU design studies are considering readout with a multiplexing factor of up to 40. We present data showing 40-row TDM readout (32 TES rows + 8 repeats of the last row) of TESs that are of the same type as those being planned for X-IFU, using measurement and analysis parameters within the ranges specified for X-IFU. Singlecolumn TDM measurements have best-fit energy resolution of (1.91 ± 0.01) eV for the Al Kα complex (1.5 keV), (2.10 ± 0.02) eV for Ti Kα (4.5 keV), (2.23 ± 0.02) eV for Mn Kα (5.9 keV), (2.40 ± 0.02) eV for Co Kα (6.9 keV), and (3.44 ± 0.04) eV for Br Kα (11.9 keV). Three-column measurements have best-fit resolution of (2.03 ± 0.01) eV for Ti Kα and (2.40 ± 0.01) eV for Co Kα. The degradation due to the multiplexed readout ranges from 0.1 eV at the lower end of the energy range to 0.5 eV at the higher end. The demonstrated performance meets X-IFU's energy-resolution and energy-range requirements. True 40-row TDM readout, without repeated rows, of kilopixel scale arrays of X-IFU-like TESs is now under development.

The risk of monozygotic twins after assisted reproductive technology: a systematic review and meta-analysis.

BACKGROUND: It is estimated that there is at least a 2-fold rise in the incidence of monozygotic twinning after assisted reproductive technology compared with natural conception. This can result in adverse pregnancy outcomes. METHODS: We searched MEDLINE, EMBASE and SCISEARCH for studies that estimated the risk of monozygotic twinning and its association with any particular assisted reproductive technique. Monozygotic twinning was defined by ultrasound or Weinberg criteria. A meta-analysis of the proportion of monozygotic twins was performed using both fixed and random effects models. RESULTS: The search revealed 37 publications reporting on the incidence of monozygotic twins after assisted reproductive techniques. Twenty-seven studies met the inclusion criteria and were included in the meta-analysis. The summary incidence of monozygotic twins after assisted conception was 0.9% (0.8-0.9%). The incidence of monozygotic twins in natural conception is 0.4%. Blastocyst transfer and intracytoplasmic sperm injection are associated with 4.25 and 2.25 times higher risk of monozygotic twins. CONCLUSIONS: The risk of monozygotic twins in assisted conception is 2.25 times higher than the natural conceptions. Larger studies reporting on monozygotic twinning following single-embryo transfer or after post-natal confirmation of zygosity with DNA analysis are warranted before definitive conclusions can be drawn and guidelines produced. In order to provide adequate pre-conceptional counselling, it is important to monitor the incidence of monozygotic twins in both natural and assisted conceptions. We suggest building a national multiple pregnancy database based on accurate diagnosis of zygosity.

Implantation, clinical pregnancy and miscarriage rates after introduction of ultrasound-guided embryo transfer.

The purpose of this study was to compare the reproductive outcome of ultrasound-guided (USG) embryo transfers versus clinical touch embryo transfers. A statistically powered retrospective analysis of women undergoing fresh and frozen embryo transfers in a National Health Service-based tertiary referral centre in the Department of Reproductive Medicine, St Mary's Hospital, Manchester was carried out. A total of 1723 embryo transfers were included in the analysis. The implantation rate was significantly higher in the USG embryo transfer group compared with the non-USG embryo transfer group (fresh: 19.9 versus 9.5%, P < 0.0001; frozen: 13.1 versus 7.3%, P < 0.0004). The clinical pregnancy rate was also significantly higher in the former group (fresh: 26.9 versus 12.5%, P < 0.0001; frozen: 15.6 versus 8.9%, P < 0.0015). For the frozen embryos, the miscarriage rate was significantly elevated among the USG embryo transfer group [unadjusted rate ratio (RR) = 1.65, 95% CI: 1.04, 2.62], but this was of borderline significance when the model was adjusted for the potential confounders (adjusted RR = 1.56, 95% CI: 0.997, 2.45). There was no difference in the ectopic pregnancy rates between the two groups. The findings of this study show that the practice of USG embryo transfer is associated with statistically higher implantation and clinical pregnancy rates in IVF.

Regulation of mouse Ah receptor (Ahr) gene basal expression by members of the Sp family of transcription factors.

The aromatic hydrocarbon receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. The mouse Ahr gene 5' proximal promoter region, which contains four potential Sp1 motifs, is required for efficient basal expression. Using a fragment spanning the region from nt -174 to +70 of the Ahr promoter, we found that four regions corresponding to four Sp1 sites were protected from DNase I digestion using nuclear extracts from MLE-12 (lung), F9 (embryonal carcinoma), Hepa-1 (hepatoma), and 41-5a (epidermal) cells. The Hepa-1 and F9 cell lines were shown by reverse transcriptase-polymerase chain reaction and Western blot to contain mRNA and protein for Sp1 and Sp3, but not Sp2 and Sp4. In electrophoretic mobility shift assays using oligonucleotide probes corresponding to the four Ahr Sp1 sites, nuclear extracts from Hepa-1 and F9 cells formed complexes that were determined immunologically to contain both Sp1 and Sp3 protein. The two Ahr proximal Sp1 sites (A and B) were shown to bind both Sp1 and Sp3 proteins, whereas the more distal sites (C and D) bound only Sp1. Competition gel shift experiments showed that sites A and B had 10-fold higher affinity for Sp factors than did sites C and D. To determine the transactivation potential of each of the four Ahr Sp1 sites, we fused the Ahr promoter to a luciferase (LUC) reporter gene and transfected the construct into the Drosophila cell line Schneider-2, which contains no Sp1 or Sp1-like factors. Cotransfection of this construct with expression plasmids for each of the Sp factors revealed that Sp3 was approximately 1.6-fold more efficient than Sp1 in Ahr transactivation. Mutation of the four Sp1 sites individually and in combination demonstrated that each site contributes to the overall level of expression of the reporter gene and that interactions between these sites play a minor role in regulation of the Ahr-LUC construct. These results suggest that basal Ahr expression may be regulated by the expression and distribution of Sp1-like factors.

Differential regulation of mouse Ah receptor gene expression in cell lines of different tissue origins.

The dioxin-binding Ah receptor (AHR) is a ligand-activated transcription factor that regulates the expression of several drug-metabolizing enzymes and has been implicated in immunosuppression, teratogenesis, cell-specific hyperplasia, and certain types of malignancies and toxicities. In order to examine tissue-specific regulation of the mouse Ah receptor gene (Ahr), we studied chimeric deletion constructs, containing the Ahr 5' flanking region and the firefly luciferase reporter gene (Luc). Transient transfection assays were performed in five established mouse cell lines: Hepa-1c1c7 (derived from hepatoma), JB6-C1 41-5a (epidermis), MLE-12 (lung epithelium), F9 (embryonal carcinoma), and NIH/3T3 (fibroblasts). Treatment of the cell lines included: dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin), retinoic acid (RA), cyclic adenosine 3':5'-monophosphate (cAMP), or 12-O-tetradecanoylphorbol 13-acetate (TPA). Expression levels of Luc varied widely from one untreated cell line to another, this finding was also confirmed by measurements of AHR mRNA steady-state levels. In all cell lines except F9 cells, maximal constitutive expression was observed with constructs containing 78 bp of Ahr promoter sequences, which include several putative binding sites for the transcription factor Sp1. In contrast, in F9 cells, inclusion of sequences between -174 and -78 resulted in a fourfold stimulation of constitutive expression, suggesting that other transcription factors are important in Ahr gene expression in these cells. In MLE-12 and 41-5a cells, expression was significantly decreased by treatment with dioxin, RA, cAMP, or TPA. A similar inhibitory effect was observed in cAMP-treated MLE-12 and F9 cells; this result was confirmed by RT-PCR measurements of AHR mRNA steady-state levels. These results indicate that both up- and down-regulation of the Ahr gene occur and exhibit tissue-and cell-type specificity.

Age related changes in the female reproductive cycle.

OBJECTIVE: To investigate the effect of age on the control of the reproductive cycle in regularly menstruating women. DESIGN: In this prospective study all women were seen regularly during both the follicular and luteal phases. Ultrasound scanning was used to confirm ovulation and measurements were taken to assess follicular development and endometrial thickness. Serum gonadotrophin levels on day 4 of the cycle, the maximum periovulatory oestradiol and progesterone on the seventh day after ovulation were measured and compared in different age groups. SUBJECTS & SETTING: Fifty-six healthy, regularly menstruating women were recruited from volunteers amongst staff of the University Hospital of South Manchester. RESULTS: Ovulation occurred later in the cycle for older women, with mean follicular phase length increasing from 13.9 days (in group 21-25 years) to 15.9 days (in group 37-45 years (P < 0.05). The mean of the maximum follicular diameter prior to rupture was significantly smaller in the older women: 16.7 mm in the 37 to 45 years old group compared with 19.6 mm, 21.6 mm and 21.3 mm in the 21 to 25, 26 to 31 and 32 to 36 years old age groups, respectively (P < 0.001). The maximum thickness of the endometrium in the luteal phase was greatest for older women: 15.9 mm in the age group 37 to 45 years compared with 12.1 mm in the age group 21 to 25 years (P < 0.001). Serum gonadotrophin concentrations during menses were higher with increased age; mean follicle stimulating hormone was 4.8 iu/l in the age group 21 to 25 years, and 8.5 iu/l in the age group 37 to 45 years (P < 0.001). Mean luteinising hormone was 4.5 iu/l in age group 21 to 25 years and 7.21 iu/l in age group 37 to 45 years (P < 0.001). Mean ovarian steroid concentrations were no different. CONCLUSIONS: These data illustrate significant age related differences in the pituitary-ovarian axis and endometrial thickness. This has implications for the management of older women in assisted reproduction and fertility control programmes.

Influence of climate on the prevalence of mania.

Monthly rates of admission of manic patients to the Department of Psychiatry in Galway Regional Hospital were examined for a five-year period. Monthly variation in admission rates was compared with monthly levels of sunshine, temperature and daylength. Results indicated a significant seasonal variation in the prevalence of mania: admission rates were higher in the sunnier months and in months with a greater average daylength. It is suggested that the presentation of mania in this fashion is due to an abnormal response to light in these patients.