A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations

BACKGROUND: Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results. Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos. METHODS: Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999. AH was performed with a diode laser. ZP thickness, opening size and embryo score were recorded. Outcome measures were implantation and delivery rates. RESULTS: Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH. Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH. CONCLUSIONS: Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion. Prescription of an immunosuppressive/antibiotic treatment is essentia

Time to Renal Disease and End-Stage Renal Disease in PROFILE: A Multiethnic Lupus Cohort

BACKGROUND: Renal involvement is a serious manifestation of systemic lupus erythematosus (SLE); it may portend a poor prognosis as it may lead to end-stage renal disease (ESRD). The purpose of this study was to determine the factors predicting the development of renal involvement and its progression to ESRD in a multi-ethnic SLE cohort (PROFILE). METHODS AND FINDINGS: PROFILE includes SLE patients from five different United States institutions. We examined at baseline the socioeconomic–demographic, clinical, and genetic variables associated with the development of renal involvement and its progression to ESRD by univariable and multivariable Cox proportional hazards regression analyses. Analyses of onset of renal involvement included only patients with renal involvement after SLE diagnosis (n = 229). Analyses of ESRD included all patients, regardless of whether renal involvement occurred before, at, or after SLE diagnosis (34 of 438 patients). In addition, we performed a multivariable logistic regression analysis of the variables associated with the development of renal involvement at any time during the course of SLE. In the time-dependent multivariable analysis, patients developing renal involvement were more likely to have more American College of Rheumatology criteria for SLE, and to be younger, hypertensive, and of African-American or Hispanic (from Texas) ethnicity. Alternative regression models were consistent with these results. In addition to greater accrued disease damage (renal damage excluded), younger age, and Hispanic ethnicity (from Texas), homozygosity for the valine allele of FcγRIIIa (FCGR3A*GG) was a significant predictor of ESRD. Results from the multivariable logistic regression model that included all cases of renal involvement were consistent with those from the Cox model. CONCLUSIONS: Fcγ receptor genotype is a risk factor for progression of renal disease to ESRD. Since the frequency distribution of FCGR3A alleles does not vary significantly among the ethnic groups studied, the additional factors underlying the ethnic disparities in renal disease progression remain to be elucidated

Beliefs, attitudes and funding of assisted reproductive technology: Public perception of over 6,000 respondents from 6 European countries

Background Fertility rates in Europe are among the lowest in the world, which may be attributed to both biological and lifestyle factors. Cost and reimbursement of fertility treatments vary across Europe, although its citizens enjoy wide access to fertility care. Since few regional studies evaluating public support for fertility treatment exist, we conducted the Listening IVF and Fertility in Europe (LIFE) survey to ascertain public perception of in vitro fertilization (IVF) and gamete donation as a treatment for infertility among European men and women. Methods and findings This survey was distributed via an online questionnaire to 8,682 individuals who were voluntary participants in an online research panel residing in France, Germany, Italy, Spain, Sweden, or the UK. The survey covered items to determine respondents’ beliefs regarding IVF and its success, the need for public funding, the use of IVF among modern families with different lifestyles, and the support for gamete donation. Results were analyzed by age, country of origin, sex, and sexual orientation. A total of 6,110 (70% of total) men and women responded. Among all respondents, 10% had undergone IVF treatment and 48% had considered or would consider IVF in case of infertility. Respondents estimated IVF mean success rate to be 47% and over half of respondents believed that availability of IVF would encourage people to delay conception. Although 93% of respondents believed that IVF treatment should be publicly funded to some extent, a majority believed that secondary infertility or use of fertility treatments allowing to delay parenthood should be financed privately. Survey respondents believed that the mean number of stimulated IVF cycles funded publicly should be limited 2 to 3 (average 2.4). 79% of respondents were willing to pay for IVF if needed with a mean amount of 5,400 € for a child brought to life through IVF. According to respondents, mean minimum and maximum ages for IVF should be 29 and 42 years old, respectively. The current survey showed support for egg and sperm donation (78%), for IVF in single women (61%) and for same-sex female couples (64%). When analyzing the results per group (i.e., sex, age, sexual orientation, and countries), youngest age groups, homosexuals, bisexuals, German respondents, and men had similar overall positive attitudes and beliefs toward IVF and opinions on public funding. Perceived limits to availability were stronger in women. Conclusion Overall, the survey results demonstrate a positive attitude among respondents in an online panel toward IVF, gamete donation, and support for public funding for fertility treatment. These findings could potentially drive discussions between patients and prescribers to explore IVF treatment and among legislators and payers to support public funding for these procedure

Eimeria Species and Genetic Background Influence the Serum Protein Profile of Broilers with Coccidiosis

BACKGROUND: Coccidiosis is an intestinal disease caused by protozoal parasites of the genus Eimeria. Despite the advent of anti-coccidial drugs and vaccines, the disease continues to result in substantial annual economic losses to the poultry industry. There is still much unknown about the host response to infection and to date there are no reports of protein profiles in the blood of Eimeria-infected animals. The objective of this study was to evaluate the serum proteome of two genetic lines of broiler chickens after infection with one of three species of Eimeria. METHODOLOGY/PRINCIPAL FINDINGS: Birds from lines A and B were either not infected or inoculated with sporulated oocysts from one of the three Eimeria strains at 15 d post-hatch. At 21 d (6 d post-infection), whole blood was collected and lesion scoring was performed. Serum was harvested and used for 2-dimensional gel electrophoresis. A total of 1,266 spots were quantitatively assessed by densitometry. Protein spots showing a significant effect of coccidia strain and/or broiler genetic line on density at P<0.05-0.01 (250 spots), P<0.01-0.001 (248 spots), and P<0.001 (314 spots) were excised and analyzed by matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry. Proteins were identified in 172 spots. A total of 46 different proteins were identified. Of the spots with a corresponding protein identification, 57 showed a main effect of coccidia infection and/or 2-way interaction of coccidia infection×broiler genetic line at P<0.001. CONCLUSIONS/SIGNIFICANCE: Several of the metabolic enzymes identified in this study are potential candidates for early diagnostic markers of E. acervulina infection including malate dehydrogenase 2, NADH dehydrogenase 1 alpha subcomplex 9, and an ATP synthase. These proteins were detected only in Line A birds that were inoculated with E. acervulina. Results from this study provide a basic framework for future research aimed at uncovering the complex biochemical mechanisms involved in host response to Eimeria infection and in identifying molecular targets for diagnostic screening and development of alternative preventative and therapeutic methods

A European multicentre prospective randomized study to assess the use of assisted hatching with a diode laser and the benefit of an immunosuppressive/antibiotic treatment in different patient populations

BACKGROUND: Assisted hatching (AH) techniques, designed for facilitating the embryo escape out of the zona pellucida (ZP) have been used in IVF centres since 1992. The initial indications for AH were patient's age, ZP thickness, high basal FSH and repeated IVF failures. Several retrospective and prospective studies assessing AH in these indications have given disparate results. Our aims were to evaluate the benefits of AH and immunosuppressive/antibiotic treatment (IA) in patients with either a poor prognosis of success, previous implantation failures or transfers of cryopreserved embryos. METHODS: Four IVF centres allocated 426 patients, randomized for AH and IA, into four groups of AH indications between 1997 and 1999. AH was performed with a diode laser. ZP thickness, opening size and embryo score were recorded. Outcome measures were implantation and delivery rates. RESULTS: Patients coming for a first or third transfer of cryopreserved embryos and poor prognosis patients admitted for a first trial did not benefit from AH. Even patients with repeated implantation failures of fresh embryos did not gain significantly from AH. CONCLUSIONS: Among AH indications, absence of implantation after several transfers of good quality embryos remains the strongest patient selection criterion. Prescription of an immunosuppressive/antibiotic treatment is essential

Immunochip analysis identifies multiple susceptibility loci for systemic sclerosis

In this study, 1,833 systemic sclerosis (SSc) cases and 3,466 controls were genotyped with the Immunochip array. Classical alleles, amino acid residues, and SNPs across the human leukocyte antigen (HLA) region were imputed and tested. These analyses resulted in a model composed of six polymorphic amino acid positions and seven SNPs that explained the observed significant associations in the region. In addition, a replication step comprising 4,017 SSc cases and 5,935 controls was carried out for several selected non-HLA variants, reaching a total of 5,850 cases and 9,401 controls of European ancestry. Following this strategy, we identified and validated three SSc risk loci, including DNASE1L3 at 3p14, the SCHIP1-IL12A locus at 3q25, and ATG5 at 6q21, as well as a suggested association of the TREH-DDX6 locus at 11q23. The associations of several previously reported SSc risk loci were validated and further refined, and the observed peak of association in PXK was related to DNASE1L3. Our study has increased the number of known genetic associations with SSc, provided further insight into the pleiotropic effects of shared autoimmune risk factors, and highlighted the power of dense mapping for detecting previously overlooked susceptibility loci

Species traits and geomorphic setting as drivers of global soil carbon stocks in seagrass meadows

Unidad de excelencia María de Maeztu CEX2019-000940-MOur knowledge of the factors that can influence the stock of organic carbon (OC) that is stored in the soil of seagrass meadows is evolving, and several causal effects have been used to explain the variation of stocks observed at local to national scales. To gain a global-scale appreciation of the drivers that cause variation in soil OC stocks, we compiled data on published species-specific traits and OC stocks from monospecific and mixed meadows at multiple geomorphological settings. Species identity was recognized as an influential driver of soil OC stocks, despite their large intraspecific variation. The most important seagrass species traits associated with OC stocks were the number of leaves per seagrass shoot, belowground biomass, leaf lifespan, aboveground biomass, leaf lignin, leaf breaking force and leaf OC plus the coastal geomorphology of the area, particularly for lagoon environments. A revised estimate of the global average soil OC stock to 20 cm depth of 15.4 Mg C ha−1 is lower than previously reported. The largest stocks were still recorded in Mediterranean seagrass meadows. Our results specifically identify Posidonia oceanica from the Mediterranean and, more generally, large and persistent species as key in providing climate regulation services, and as priority species for conservation for this specific ecosystem service

Controlling liver cancer internationally: A qualitative study of clinicians' perceptions of current public policy needs

<p>Abstract</p> <p>Background</p> <p>Liver cancer is the fifth most common cancer in men and the seventh for women. Usually because of late diagnosis, the prognosis for liver cancer remains poor, resulting in liver cancer being the third most common cause of death from cancer. While some countries have treatment guidelines, little is known or understood about the strategies needed for liver cancer control internationally.</p> <p>Objective</p> <p>To explore leading liver cancer clinician's perceptions of the current public policy needs to control liver cancer internationally.</p> <p>Methods</p> <p>Key informant interviews were conducted with a range of liver cancer clinicians involved in policy in eleven countries. Interviews were digitally recorded, transcribed verbatim, translated (where necessary), de-identified and analyzed by two researchers using a constant comparative method.</p> <p>Results</p> <p>Twenty in-depth semi-structured interviews were conducted in: Australia, China, France, Germany, Italy, Japan, Spain, South Korea, Taiwan, Turkey and the United States. Nine themes were identified and cluster into three groups: 1) Promoting prevention via early risk assessment, focusing on viral hepatitis and other lifestyle factors; 2) Increasing political, public and medical community awareness; and 3) Improving funding for screening, liver cancer surveillance and treatment.</p> <p>Conclusion</p> <p>This study is an important step towards developing an evidence-based approach to assessing preparedness for implementing comprehensive liver cancer control strategies. Evaluation mechanisms to assess countries' performance on the needs described are needed. Future research will concentrate of understanding how these needs vary across countries and the optimal strategies to improve the diagnosis and prognosis of patients with liver cancer internationally.</p

Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: Results from the scleroderma lung study

Objective To assess the impact of cyclophosphamide (CYC) on the health-related quality of life (HRQOL) of patients with scleroderma after 12 months of treatment. Methods One hundred fifty-eight subjects participated in the Scleroderma Lung Study, with 79 each randomized to CYC and placebo arms. The study evaluated the results of 3 measures of health status: the Short Form 36 (SF-36), the Health Assessment Questionnaire (HAQ) disability index (DI), and Mahler's dyspnea index, and the results of 1 preference-based measure, the SF-6D. The differences in the HRQOL between the 2 groups at 12 months were calculated using a linear mixed model. Responsiveness was evaluated using the effect size. The proportion of subjects in each treatment group whose scores improved at least as much as or more than the minimum clinically important difference (MCID) in HRQOL measures was assessed. Results After adjustment for baseline scores, differences in the HAQ DI, SF-36 role physical, general health, vitality, role emotional, mental health scales, and SF-36 mental component summary (MCS) score were statistically significant for CYC versus placebo ( P < 0.05). Effect sizes were negligible (<0.20) for all of the scales of the SF-36, HAQ DI, and SF-6D at 12 months. In contrast, a higher proportion of patients who received CYC achieved the MCID compared with placebo in the HAQ DI score (30.9% versus 14.8%), transitional dyspnea index score (46.4% versus 12.7%), SF-36 MCS score (33.3% versus 18.5%), and SF-6D score (21.3% versus 3.8%). Conclusion One year of treatment with CYC leads to an improvement in HRQOL in patients with scleroderma lung disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/56039/1/22580_ftp.pd

Identifying important breast cancer control strategies in Asia, Latin America and the Middle East/North Africa

Background: Breast cancer is the most frequent cause of cancer death in women worldwide, but global disparities in breast cancer control persist, due to a lack of a comprehensive breast cancer control strategy in many countries. Objectives: To identify and compare the need for breast cancer control strategies in Asia, Latin America and the Middle East/North Africa and to develop a common framework to guide the development of national breast cancer control strategies. Methods: Data were derived from open-ended, semi-structured interviews conducted in 2007 with 221 clinicians, policy makers, and patient advocates; stratified across Asia (n = 97), Latin America (n = 46), the Middle East/North Africa (ME/NA) (n = 39) and Australia and Canada (n = 39). Respondents were identified using purposive and snowballing sampling. Interpretation of the data utilized interpretive phenomenological analysis where transcripts and field notes were coded and analyzed and common themes were identified. Analysis of regional variation was conducted based on the frequency of discussion and the writing of the manuscript followed the RATS guidelines. Results: Analysis revealed four major themes that form the foundation for developing national breast cancer control strategies: 1) building capacity; 2) developing evidence; 3) removing barriers; and 4) promoting advocacy - each specified across five sub-ordinate dimensions. The propensity to discuss most dimensions was similar across regions, but managing advocacy was discussed more frequently (p = 0.004) and organized advocacy was discussed less frequently (p \u3c 0.001) in Australia and Canada. Conclusions: This unique research identified common themes for the development of breast cancer control strategies, grounded in the experience of local practitioners, policy makers and advocacy leaders across diverse regions. Future research should be aimed at gathering a wider array of experiences, including those of patients