Defining critical factors in multi-country studies of assisted reproductive technologies (ART): data from the US and UK health systems

As the worldwide use of assisted reproductive technologies (ART) continues to grow, there is a critical need to assess the safety of these treatment parameters and the potential adverse health effects of their use in adults and their offspring. While key elements remain similar across nations, geographic variations both in treatments and populations make generalizability challenging. We describe and compare the demographic factors between the USA and the UK related to ART use and discuss implications for research. The USA and the UK share some common elements of ART practice and in how data are collected regarding long-term outcomes. However, the monitoring of ART in these two countries each brings strengths that complement each other’s limitations

The association of impaired semen quality and pregnancy rates in assisted reproduction technology cycles: Systematic review and meta-analysis

Some studies suggest a relationship between semen quality and pregnancy rates of assisted reproduction technologies (ART). Others have questioned the utility of semen quality as proxy for fertility in couples attempting to conceive with or without assistance. We aimed to investigate the current body of evidence which correlates semen parameters and clinical pregnancy among couples utilizing ART (i.e. in vitro fertilization [IVF], intracytoplasmic sperm injection [ICSI]) through a systematic review and meta-analysis of cross-sectional and retrospective cohort studies. Pooled Odd Ratio (OR) for oligo-, astheno- and teratospermic compared to normospermic number of ART cycles were calculated among. Meta-regression and sub-group analysis were implemented to model the contribution of clinical/demographic and laboratory standards differences among the studies. Overall, 17 studies were analysed representing 17,348 cycles were analysed. Pooled OR for impaired sperm concentration, motility and morphology was 1 (95%Confidence Interval [CI]: 0.97-1.03), 0.88 (95%CI: 0.73-1.03) and 0.88 (95%CI: 0.75-1) respectively. Further analysis on sperm morphology showed no differences with regard of IVF versus ICSI (p = 0.14) nor a significant correlation with rising reference thresholds (Coeff: -0.02, p = 0.38). A temporal trend towards a null association between semen parameters and clinical pregnancy was observed over the 20-year observation period (Coeff: 0.01, p = 0.014). The current analysis found no association between semen quality (as measured by concentration, motility or morphology) and clinical pregnancy rates utilizing ART. Future investigations are necessary to explore the association between semen parameters and other ART outcomes (e.g. fertilization, implantation, birth and perinatal health)

Efficacy of three BCG strains (Connaught, TICE and RIVM) with or without secondary resection (re-TUR) for intermediate/high-risk non-muscle-invasive bladder cancers: results from a retrospective single-institution cohort analysis

Purpose: (I) To evaluate the clinical efficacy of three different BCG strains in patients with intermediate-/high-risk non-muscle-invasive bladder cancer (NMIBC). (II) To determine the importance of performing routine secondary resection (re-TUR) in the setting of BCG maintenance protocol for the three strains. Methods: NMIBCs who received an adjuvant induction followed by a maintenance schedule of intravesical immunotherapy with BCG Connaught, TICE and RIVM. Only BCG-naïve and those treated with the same strain over the course of follow-up were included. Cox proportional hazards model was developed according to prognostic factors by the Spanish Urological Oncology Group (CUETO) as well as by adjusting for the implementation of re-TUR. Results: n = 422 Ta-T1 patients (Connaught, n = 146; TICE, n = 112 and RIVM, n = 164) with a median (IQR) follow-up of 72 (60-85) were reviewed. Re-TUR was associated with improved recurrence and progression outcomes (HRRFS: 0.63; 95% CI 0.46-0.86; HRPFS: 0.55; 95% CI 0.31-0.86). Adjusting for CUETO risk factors and re-TUR, BGC TICE and RIVM provided longer RFS compared to Connaught (HRTICE: 0.58, 95% CI 0.39-0.86; HRRIVM: 0.61, 95% CI 0.42-0.87) while no differences were identified between strains for PFS and CSS. Sub-analysis of only re-TUR cases (n = 190, 45%) showed TICE the sole to achieve longer RFS compared to both Connaught and RIVM. Conclusion: Re-TUR was confirmed to ensure longer RFS and PFS in intermediate-/high-risk NMIBCs but did not influence the relative single BCG strain efficacy. When routinely performing re-TUR followed by a maintenance BCG schedule, TICE was superior to the other strains for RFS outcomes

Electrochemical synthesis of peroxomonophosphate using boron-doped diamond anodes

A new method for the synthesis of peroxomonophosphate, based on the use of boron-doped diamond electrodes, is described. The amount of oxidant electrogenerated depends on the characteristics of the supporting media (pH and solute concentration) and on the operating conditions (temperature and current density). Results show that the pH, between values of 1 and 5, does not influence either the electrosynthesis of peroxomonophosphate or the chemical stability of the oxidant generated. Conversely, low temperatures are required during the electrosynthesis process to minimize the thermal decomposition of peroxomonophosphate and to guarantee significant oxidant concentration. In addition, a marked influence of both the current density and the initial substrate is observed. This observation can be explained in terms of the contribution of hydroxyl radicals in the oxidation mechanisms that occur on diamond surfaces. In the assays carried out below the water oxidation potential, the generation of hydroxyl radicals did not take place. In these cases, peroxomonophosphate generation occurs through a direct electron transfer and, therefore, at these low current densities lower concentrations are obtained. On the other hand, at higher potentials both direct and hydroxyl radical-mediated mechanisms contribute to the oxidant generation and the process is more efficient. In the same way, the contribution of hydroxyl radicals may also help to explain the significant influence of the substrate concentration. Thus, the coexistence of both phosphate and hydroxyl radicals is required to ensure the generation of significant amounts of peroxomonophosphoric acid

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation

A retrospective study of cochlear implant outcomes in children with residual hearing

BACKGROUND: There has been increasing demand for the cochlear implantation of children who demonstrate some auditory capacity with conventional hearing aids. The purpose of this study was to examine speech recognition outcomes in a group of children who were regarded as borderline candidates for cochlear implantation as their residual hearing and/or auditory functioning levels exceeded typical audiologic candidacy criteria. METHODS: A retrospective chart review was undertaken at one Canadian cochlear implant centre to identify children implanted at age 4 or older with a pure-tone-average of 90 dB or better and speech recognition of 30% or greater. Pre-implant and post-implant open-set word and sentence test scores were analyzed. RESULTS: Eleven children of 195 paediatric cochlear implant recipients met the inclusion criteria for this study. Speech recognition results for the10 English-speaking children indicated significant gains in both open-set word and sentence understanding within the first 6 to 12 months of implant use. Seven of 9 children achieved 80% open-set sentence recognition within 12 months post-surgery. CONCLUSION: Children with several years of experience using conventional amplification demonstrated rapid progress in auditory skills following cochlear implantation. These findings suggest that cochlear implantation may be an appropriate intervention for selected children with severe hearing losses and/or auditory capacity outside current candidacy criteria

Dose patterns in commercially insured subjects chronically exposed to opioids: a large cohort study in the United States

<p>Abstract</p> <p>Background</p> <p>Little data exist on how opioid doses vary with the length of exposure among chronic opioid users.</p> <p>Methods</p> <p>To characterize the change in the dosage of opioids over time, a retrospective cohort study using the PharMetrics database for the years 1999 through 2008 was conducted. Individuals exposed to opioids in 2000 who had 2 opioid dispensings at least 6 months apart and were opioid naive (did not receive any opioid 6 month before their exposure in 2000) were included. The date of the first dispensing in 2000 was defined as the index date and the dispensing had to be for a strong and full agonist opioid. All opioid doses were converted to oral morphine equivalent doses. Exposure was classified as continuous or intermittent. Mean, median, interquartile range, and 95^thpercentile of opioid dose over 6-month periods, as well as the percentage of subjects who ever received a high or very high opioid dose, were calculated.</p> <p>Results</p> <p>Among the 48,986 subjects, the mean age was 44.5 years and 54.5% were women. Intermittent exposure was observed in 99% of subjects; continuous exposure was observed in 1% of subjects. The mean duration of exposure for the subjects who were continuously exposed to opioids was 477 days. In subjects with no cancer diagnosis who were continuously exposed to opioids, the mean, 25^th, 50^th, and 75^thpercentile of dose was stable during the first 2 years of use, but the 95^thpercentile increased. Seven percent of them were exposed to doses of 180 mg or more of morphine at some point.</p> <p>Conclusions</p> <p>Dose escalation is uncommon in subjects with intermittent exposure to opioids. For subjects with continuous exposure to opioids who have cancer, doses rise substantially with time. For those without cancer, doses remain relatively stable for the first 2 years of use, but subsequently increase. Seven percent of subjects with no cancer diagnosis will be exposed to daily doses of 180 mg or more of morphine equivalent at some point.</p

Herbal medicine use during pregnancy in a group of Australian women

BACKGROUND: There are limited data on the extent of women's use of herbal medicines during pregnancy, despite the fact that knowledge of the potential benefits or harms of many of these products is sparse, particularly with respect to their use in pregnancy. We aimed to measure the prevalence of herbal medicine use in a group of pregnant women attending a public tertiary maternity hospital in Melbourne, Australia. Secondary aims were to explore why women took the herbal medicine, where they received advice, what form the supplements took and if they perceived the supplements to be helpful. METHODS: Consecutive pregnant women were approached in the antenatal clinic and the birth centre at around 36–38 weeks gestation. A questionnaire was developed and self-administered in English, as well as being translated into the four most common languages of women attending the hospital: Cantonese, Vietnamese, Turkish and Arabic. Back translation into English was undertaken by different professional translators to verify accuracy of both words and concepts. Data collected included demographic information, model of pregnancy care and herbal supplement use. Descriptive statistics were used initially, with stratified and regression analysis to compare sub-groups. RESULTS: Of 705 eligible women, 588 (83%) agreed to participate. Of these, 88 (15%) completed the questionnaire in a language other than English. Thirty-six percent of women took at least one herbal supplement during the current pregnancy. The most common supplements taken were raspberry leaf (14%), ginger (12%) and chamomile (11%). Women were more likely to take herbal supplements if they were older, tertiary educated, English speaking, non-smokers and primiparous. CONCLUSION: Use of herbal supplements in pregnancy is likely to be relatively high and it is important to ascertain what supplements (if any) women are taking. Pregnancy care providers should be aware of the common herbal supplements used by women, and of the evidence regarding potential benefits or harm

Angular and Current-Target Correlations in Deep Inelastic Scattering at HERA

Correlations between charged particles in deep inelastic ep scattering have been studied in the Breit frame with the ZEUS detector at HERA using an integrated luminosity of 6.4 pb-1. Short-range correlations are analysed in terms of the angular separation between current-region particles within a cone centred around the virtual photon axis. Long-range correlations between the current and target regions have also been measured. The data support predictions for the scaling behaviour of the angular correlations at high Q2 and for anti-correlations between the current and target regions over a large range in Q2 and in the Bjorken scaling variable x. Analytic QCD calculations and Monte Carlo models correctly describe the trends of the data at high Q2, but show quantitative discrepancies. The data show differences between the correlations in deep inelastic scattering and e+e- annihilation.Comment: 26 pages including 10 figures (submitted to Eur. J. Phys. C

Plastisol Foaming Process. Decomposition of the Foaming Agent, Polymer Behavior in the Corresponding Temperature Range and Resulting Foam Properties

The decomposition of azodicarbonamide, used as foaming agent in PVC - plasticizer (1/1) plastisols was studied by DSC. Nineteen different plasticizers, all belonging to the ester family, two being polymeric (polyadipates), were compared. The temperature of maximum decomposition rate (in anisothermal regime at 5 K min-1 scanning rate), ranges between 434 and 452 K. The heat of decomposition ranges between 8.7 and 12.5 J g -1. Some trends of variation of these parameters appear significant and are discussed in terms of solvent (matrix) and viscosity effects on the decomposition reactions. The shear modulus at 1 Hz frequency was determined at the temperature of maximum rate of foaming agent decomposition, and differs significantly from a sample to another. The foam density was determined at ambient temperature and the volume fraction of bubbles was used as criterion to judge the efficiency of the foaming process. The results reveal the existence of an optimal shear modulus of the order of 2 kPa that corresponds roughly to plasticizer molar masses of the order of 450 ± 50 g mol-1. Heavier plasticizers, especially polymeric ones are too difficult to deform. Lighter plasticizers such as diethyl phthalate (DEP) deform too easily and presumably facilitate bubble collapse