•Follitropin delta was individualized based on anti-Müllerian hormone concentration and body weight in Japanese women.•Non-inferiority was shown between follitropin delta and beta in terms of number ...of oocytes.•Individualized dosing significantly reduced rates of ovarian hyperstimulation syndrome.•Individualized dosing showed a favourable benefit–risk profile in fresh cycles.
This study aimed to establish the efficacy and safety of ovarian stimulation with a follitropin delta individualized fixed-dose regimen based on serum anti-Müllerian hormone (AMH) concentration and body weight versus conventional follitropin beta dosing in Japanese women.
This randomized, controlled, assessor-blind, multicentre, non-inferiority trial was conducted in 347 Japanese IVF/intracytoplasmic sperm injection patients. They were randomized to individualized follitropin delta (AMH <15 pmol/l: 12 µg/day; AMH ≥15 pmol/l: 0.10–0.19 µg/kg/day; minimum 6 µg/day; maximum 12 µg/day) or conventional follitropin beta (150 IU/day for the first 5 days, with potential subsequent dose adjustments). The primary end-point was the number of oocytes retrieved with a pre-specified non-inferiority margin (−3.0 oocytes).
The primary trial objective was met, as non-inferiority was established for number of oocytes retrieved for individualized follitropin delta dosing compared with conventional follitropin beta dosing (9.3 versus 10.5; lower boundary of 95% confidence interval −2.3). The occurrence of ovarian hyperstimulation syndrome (OHSS) was reduced to approximately half with individualized compared with conventional dosing, with an incidence of 11.2% versus 19.8% (P = 0.021) for OHSS of any grade and 7.1% versus 14.1% (P = 0.027) for moderate/severe OHSS. The live birth rate per started cycle was 23.5% for individualized dosing and 18.6% for conventional dosing.
Dosing with individualized follitropin delta in Japanese women is non-inferior to conventional dosing with follitropin beta for number of oocytes retrieved. The individualized approach shows a favourable benefit–risk profile, providing a statistically significant and clinically relevant reduction in the incidence of OHSS, without compromising live birth rates.
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Background & Aims Alcoholic hepatitis (AH) is characterized by hepatocellular damage, inflammation, and fibrosis. We performed a prospective study to associate hepatic expression of the CXC subfamily ...of chemokines with histology findings and prognosis of patients with AH. Methods Liver biopsy samples from 105 patients with AH and 5 normal liver samples (controls) were evaluated for steatosis, inflammation, fibrosis, and cholestasis. Computer-based morphometric analysis assessed the numbers of infiltrating CD3 + T cells and CD15 + cells (neutrophils); terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling staining was used to quantify apoptosis. Expression of CXC and CC chemokines and selected signaling components were assessed by quantitative reverse-transcription polymerase chain reaction; protein levels of interleukin (IL)-8 and Gro-α also were determined by immunohistochemistry. Serum levels of IL-8 and Gro-α were measured by enzyme-linked immunosorbent assay. The Cox regression model identified variables associated with mortality. Results Most patients (75%) had severe AH; their 90-day mortality rate was 21.9%. In AH liver samples, expression of the CXC subfamily members IL-8, Gro-α, CXCL5, CXCL6, CXCL10, and platelet factor 4 was up-regulated and compared with controls. The CC chemokine CCL2, but not CCL5, also was up-regulated. Higher expression levels of IL- 8, CXCL5, Gro-γ, and CXCL6 were associated with worse prognosis. Expression of CXC components correlated with neutrophil infiltration and the severity of portal hypertension. In the multivariate analysis, IL-8 protein levels were an independent predictor of 90-day mortality. IL-8 and Gro-α serum levels did not correlate with prognosis. Conclusions Hepatic expression of CXC components correlates with prognosis of patients with AH. Reagents that target CXC chemokines might be developed as therapeutics.
Potential explanations point to a lack of pandemic preparedness (ie, weak surveillance systems, low capacity for PCR tests, and scarcity of personal protective equipment and critical care equipment), ...a delayed reaction by central and regional authorities, slow decision-making processes, high levels of population mobility and migration, poor coordination among central and regional authorities, low reliance on scientific advice, an ageing population, vulnerable groups experiencing health and social inequalities, and a lack of preparedness in nursing homes. ...the social and economic circumstances that have contributed to making Spain more vulnerable, including rising inequalities, must be considered. Specific concerns include public health functions, leadership and governance, financing, health and social workforce, health information systems, service delivery, access to diagnosis and treatment, the role of scientific research, and the experience and values of individuals, communities, and vulnerable groups.
Male factor infertility is increasing and recognized as playing a key role in reproductive health and disease. The current primary diagnostic approach is to assess sperm quality associated with ...reduced sperm number and motility, which has been historically of limited success in separating fertile from infertile males. The current study was designed to develop a molecular analysis to identify male idiopathic infertility using genome wide alterations in sperm DNA methylation. A signature of differential DNA methylation regions (DMRs) was identified to be associated with male idiopathic infertility patients. A promising therapeutic treatment of male infertility is the use of follicle stimulating hormone (FSH) analogs which improved sperm numbers and motility in a sub-population of infertility patients. The current study also identified genome-wide DMRs that were associated with the patients that were responsive to FSH therapy versus those that were non-responsive. This novel use of epigenetic biomarkers to identify responsive versus non-responsive patient populations is anticipated to dramatically improve clinical trials and facilitate therapeutic treatment of male infertility patients. The use of epigenetic biomarkers for disease and therapeutic responsiveness is anticipated to be applicable for other medical conditions.
Abstract
The Integrated Microbial Genome/Virus (IMG/VR) system v.2.0 (https://img.jgi.doe.gov/vr/) is the largest publicly available data management and analysis platform dedicated to viral genomics. ...Since the last report published in the 2016, NAR Database Issue, the data has tripled in size and currently contains genomes of 8389 cultivated reference viruses, 12 498 previously published curated prophages derived from cultivated microbial isolates, and 735 112 viral genomic fragments computationally predicted from assembled shotgun metagenomes. Nearly 60% of the viral genomes and genome fragments are clustered into 110 384 viral Operational Taxonomic Units (vOTUs) with two or more members. To improve data quality and predictions of host specificity, IMG/VR v.2.0 now separates prokaryotic and eukaryotic viruses, utilizes known prophage sequences to improve taxonomic assignments, and provides viral genome quality scores based on the estimated genome completeness. New features also include enhanced BLAST search capabilities for external queries. Finally, geographic map visualization to locate user-selected viral genomes or genome fragments has been implemented and download options have been extended. All of these features make IMG/VR v.2.0 a key resource for the study of viruses.
Purpose
The purpose of this paper is to analyze Spain’s success in developing mass tourism between 1950 and 1965.
Design/methodology/approach
This analysis will be carried out from a marketing point ...of view using the paradigm of the four Ps: product, price, promotion and place, but focusing on the product since, as will be seen, the three other variables had a much lesser impact at that early stage. The product, in holiday tourism, is the destination, a combination in which the main protagonist is the hotel. The authors will analyse the main characteristics of the tourist accommodation on offer in Majorca and Ibiza in two ways: by studying the general statistics on the one hand, and on the other, through the detailed description of two hotel projects focused on the same tourist market but conceptually very different. In the first, a British design from 1956, we see the seed of what could have been and was not. Spain could have been filled with enclave-type tourist destinations with little connection to the local economic network. The second hotel design, on the other hand, shows us the ideal establishment for the exploitation of mass tourism in open destinations.
Findings
In Spain, mass tourism was explosively successful because the local business community was able to offer a very attractive product.
Originality/value
The authors use the architectural designs of two hotels as the central axis of the description of the Spanish tourism product.
Anal intercourse (AI) among heterosexuals is an understudied and taboo subject. This 2017 Swiss national study aimed to describe the characteristics and motivations of heterosexual young adults ...practicing AI. Participants with any same-sex experience, same-sex attraction or non-heterosexual identity were excluded. The Federal Statistical Office provided the initial sample and potential participants were recruited through postal mail inviting them to an online survey (response rate 15.1%). The sample comprised 3892 participants (52% males; 54% of the overall sample, mean age 26.3 years). Overall, 55% of women and 56% of men had never experienced AI, 17% and 12% had done it once and 28% and 32% more than once, respectively. We found that participants engaging in AI had higher odds of practicing intercourse while intoxicated, being younger at first sexual experience, not using a condom at last intercourse and reporting a history of sexual transmitted infections. The main reason reported by both genders for engaging in their first AI was being curious followed by being in love. In conclusion, AI is a widespread practice among heterosexual young adults and health professionals should be especially attentive to it.
The objective of this study was to compare the frequency of risk behaviors and to measure the extent of co-occurrence of these behaviors in chronically ill and healthy adolescents.
Data were drawn ...from the 2002 Swiss Multicenter Adolescent Survey on Health database, a nationally representative survey of 7548 adolescents in postmandatory school aged 16 to 20 years. There were 760 subjects who reported a chronic illness and/or a disability. The comparison group consisted of 6493 subjects who answered negatively to both questions. We defined 8 risk behaviors: daily smoking, alcohol misuse, current cannabis use, current use of any other illegal drug, early sexual debut, eating disorder, violent acts, and antisocial acts. We analyzed each behavior and the sum of behaviors, controlling for age, gender, academic track, parents' education level, depression, and health status. Results are given as adjusted odds ratios using the comparison group as the reference category.
Youth with a chronic condition were more likely to smoke daily, to be current cannabis users, and to have performed violent or antisocial acts. Youth with a chronic condition were also more likely to report 3 or >or=4 risk behaviors.
These results indicate that having a chronic condition carries additional risks for engaging in health risk behaviors and emphasize the importance of health risk screening and preventive counseling for young people in general and among those suffering from chronic conditions in particular.
To compare the efficacy and safety of follitropin delta, a new human recombinant FSH with individualized dosing based on serum antimüllerian hormone (AMH) and body weight, with conventional ...follitropin alfa dosing for ovarian stimulation in women undergoing IVF.
Randomized, multicenter, assessor-blinded, noninferiority trial (ESTHER-1).
Reproductive medicine clinics.
A total of 1,329 women (aged 18–40 years).
Follitropin delta (AMH <15 pmol/L: 12 μg/d; AMH ≥15 pmol/L: 0.10–0.19 μg/kg/d; maximum 12 μg/d), or follitropin alfa (150 IU/d for 5 days, potential subsequent dose adjustments; maximum 450 IU/d).
Ongoing pregnancy and ongoing implantation rates; noninferiority margins −8.0%.
Ongoing pregnancy (30.7% vs. 31.6%; difference −0.9% 95% confidence interval (CI) −5.9% to 4.1%), ongoing implantation (35.2% vs. 35.8%; −0.6% 95% CI −6.1% to 4.8%), and live birth (29.8% vs. 30.7%; −0.9% 95% CI −5.8% to 4.0%) rates were similar for individualized follitropin delta and conventional follitropin alfa. Individualized follitropin delta resulted in more women with target response (8–14 oocytes) (43.3% vs. 38.4%), fewer poor responses (fewer than four oocytes in patients with AMH <15 pmol/L) (11.8% vs. 17.9%), fewer excessive responses (≥15 or ≥20 oocytes in patients with AMH ≥15 pmol/L) (27.9% vs. 35.1% and 10.1% vs. 15.6%, respectively), and fewer measures taken to prevent ovarian hyperstimulation syndrome (2.3% vs. 4.5%), despite similar oocyte yield (10.0 ± 5.6 vs. 10.4 ± 6.5) and similar blastocyst numbers (3.3 ± 2.8 vs. 3.5 ± 3.2), and less gonadotropin use (90.0 ± 25.3 vs. 103.7 ± 33.6 μg).
Optimizing ovarian response in IVF by individualized dosing according to pretreatment patient characteristics results in similar efficacy and improved safety compared with conventional ovarian stimulation.
NCT01956110.
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