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The United Nations refers to South-South cooperation as a broad framework of collaboration between developing countries in the Global South. It can take place on a bilateral, regional, or interregional basis. Its main purpose is to share knowledge, skills, resources and successful initiatives to meet development goals through concerted partnerships. Triangular cooperation implies the presence of traditional donor countries and organizations which facilitate South-South initiatives. Both forms of cooperation carry distinct benefits and differ from the more traditional North-South partnerships. This presentation will describe how, under the umbrella and support of ICMART, regional and interregional ART registries in the developing South, specifically the Latin American registry (REDLARA) and the African registry (ANARA), are contributing to the development, sustainability and cohesion in ART monitoring among the many countries they represent. With an innovative and standardized ART registry as a backbone, 35 countries in these two continents are now organized in regional reproductive networks increasing their recognition, visibility and impact, We shall demonstrate that this south-south and triangular cooperation, built upon a spirit of community and regional belonging is a strong facilitator of ART monitoring and transfer of technology to the developing South, and its ongoing expansion and reach. In Latin America, where REDLARA was established 30 years ago, local and expedited channels of communication have furthermore underpinned the training of embryologists, clinicians and other health care professionals through regional networks of professionals and certified training centers. This has resulted in enhanced ART self-reliance including the capability to implement new ART technologies and also monitor their availability, utilization, effectiveness and safety. Similar initiatives, strongly supported by REDLARA and ICMART, are starting to be implemented among African institutions via ANARA. Lastly, we shall demonstrate that our regional as well as global ART registries, together with other international organizations, have contributed to the dissemination of knowledge and serve as monitors and external quality controls now for 35 countries and almost 300 institutions in Latin America and Africa. Furthermore, given that both continents are progressively implementing the same cycle-based reporting system, new knowledge will be gained by examining regional and country similarities and differences.

Abstract title International Committee for Monitoring Assisted Reproductive Technologies (ICMART) Preliminary World Report on ART, 2018 Study question In 2018 what was global utilization, effectiveness and safety of ART? Summary answer Globally, ART utilization and data collection continue to increase but with wide variations in utilization, effectiveness and safety. What is known already ICMART began ART global data collection in 1991. Utilization, effectiveness and safety have continuously improved with more cycles, higher pregnancy rates and lower multiple birth rates, the latter as a result of transfer of fewer embryos. Frozen embryo transfer (FET) and donor egg cycles continue to increase. However, wide variations in practice and outcomes exist globally. Approximately 9 million ART babies have been born. ICMART has helped develop registries internationally. A new electronic data collection platform has been developed in conjunction with the University of New South Wales in Sydney, Australia; nevertheless, data collection and quality remain challenging. Study design, size, duration Countries and regions annually collect ART data, some prospectively and others retrospectively. ICMART retrospectively requested these data from all known global sources for 2018 and reviewed them for missing or incorrect data. The dataset was corrected and then analyzed utilizing standardized definitions from The ICMART/WHO Revised Glossary on ART Terminology, 2009 which was current at the time but is now replaced by The International Glossary on Infertility and Fertility Care, 2017, and previously developed methods. Preliminary results are presented. Participants/materials, setting, methods The European IVF Monitoring Consortium (EIM), Latin American Network of Assisted Reproduction (REDLARA), Australian/ New Zealand Registry and African Network and Registry for ART (ANARA) submitted regional data, and other countries contributed national data, through standardized formats to ICMART. A few individual clinics with no registry access also contributed. Data were reviewed, corrected, validated to the extent possible, analyzed and summarized by ICMART using descriptive statistics. Main results and the role of chance Data collection and analysis are ongoing, so presented results are preliminary. The number of ART cycles continues to increase, but utilization is still highly variable among countries and regions. Regional and country differences persist in the age of women treated, number of embryos transferred, live birth rates, rate of multiple births, use of ICSI, cryopreservation cycles and other factors. The role of chance is minimal. Actual global ART results are limited to reporting countries and clinics representing approximately 3/4 of global cycles. However, this is a very large sample size from which imputation of total global results is performed. Limitations, reasons for caution Some countries have limited data and many countries have limited data validation. ICMART can perform only minimal verification of submitted data. Widespread adherence to consensus definitions provided in the Glossary takes time and requires translation into multiple languages. Wider implications of the findings ICMART World Reports standardize data, track trends, enable comparisons, stimulate questions and improve ART quality. Better understanding of ART increases societal acceptance and support for equitable access and ART research.

STUDY QUESTION What is the recommended management for medically assisted reproduction (MAR) in patients with a viral infection or disease, based on the best available evidence in the literature? SUMMARY ANSWER The ESHRE guideline on MAR in patients with a viral infection/disease makes 78 recommendations on prevention of horizontal and vertical transmission before, during and after MAR, and the impact on its outcomes, and these also include recommendations regarding laboratory safety on the processing and storage of gametes and embryos testing positive for viral infections. WHAT IS KNOWN ALREADY The development of new and improved anti-viral medications has resulted in improved life expectancy and quality of life for patients with viral infections/diseases. Patients of reproductive age are increasingly exploring their options for family creation. STUDY DESIGN, SIZE, DURATION The guideline was developed according to the structured methodology for the development of ESHRE guidelines. After the formulation of nine key questions for six viruses (hepatitis B virus, hepatitis C virus, human immunodeficiency virus, human papilloma virus, human T-lymphotropic virus I/II and Zika virus) by a group of experts, literature searches and assessments were performed. Papers published up to 2 November 2020 and written in English were included in the review. Evidence was analyzed by female, male or couple testing positive for the virus. PARTICIPANTS/MATERIALS, SETTING, METHODS Based on the collected evidence, recommendations were formulated and discussed until consensus was reached within the guideline group. There were 61 key questions to be answered by the guideline development group (GDG), of which 12 were answered as narrative questions and 49 as PICO (Patient, Intervention, Comparison, Outcome) questions. A stakeholder review was organized after the finalization of the draft. The final version was approved by the GDG and the ESHRE Executive Committee. MAIN RESULTS AND THE ROLE OF CHANCE This guideline aims to help providers meet a growing demand for guidance on the management of patients with a viral infection/disease presenting in the fertility clinic. The guideline makes 78 recommendations on prevention of viral transmission before and during MAR, and interventions to reduce/avoid vertical transmission to the newborn. Preferred MAR treatments and interventions are described together with the effect of viral infections on outcomes. The GDG formulated 44 evidence-based recommendations—of which 37 were formulated as strong recommendations and 7 as weak—33 good practice points (GPP) and one research only recommendation. Of the evidence-based recommendations, none were supported by high-quality evidence, two by moderate-quality evidence, 15 by low-quality evidence and 27 by very low-quality evidence. To support future research in the field of MAR in patients with a viral infection/disease, a list of research recommendations is provided. LIMITATIONS, REASONS FOR CAUTION Most interventions included are not well-studied in patients with a viral infection/disease. For a large proportion of interventions, evidence was very limited and of very low quality. More evidence is required for these interventions, especially in the field of human papilloma virus (HPV). Such future studies may require the current recommendations to be revised. WIDER IMPLICATIONS OF THE FINDINGS The guideline provides clinicians with clear advice on best practice in MAR for patients with a viral infection/disease, based on the best evidence currently available. In addition, a list of research recommendations is provided to stimulate further studies in the field. STUDY FUNDING/COMPETING INTEREST(S) The guideline was developed and funded by ESHRE, covering expenses associated with the guideline meetings, with the literature searches and with the dissemination of the guideline. The guideline group members did not receive any financial incentives, all work was provided voluntarily. A.D. reports research fees from Ferring and Merck, consulting fees from Ferring, outside the submitted work. C.P. reports speakers fees from Merck and MSD outside the submitted work. K.T. reports speakers fees from Cooper Surgical and Ferring and consultancy fees as member of the advisory board BioTeam of Ferring, outside the submitted work. The other authors have no conflicts of interest to declare. DISCLAIMER This guideline represents the views of ESHRE, which were achieved after careful consideration of the scientific evidence available at the time of preparation. In the absence of scientific evidence on certain aspects, a consensus between the relevant ESHRE stakeholders has been obtained. Adherence to these clinical practice guidelines does not guarantee a successful or specific outcome, nor does it establish a standard of care. Clinical practice guidelines do not replace the need for application of clinical judgment to each individual presentation, nor variations based on locality and facility type. ESHRE makes no warranty, express or implied, regarding the clinical practice guidelines and specifically excludes any warranties of merchantability and fitness for a particular use or purpose. (Full disclaimer available at www.eshre.eu/guidelines.)

Bipolar disorder is a heritable mental illness with complex etiology. We performed a genome-wide association study of 41,917 bipolar disorder cases and 371,549 controls of European ancestry, which identified 64 associated genomic loci. Bipolar disorder risk alleles were enriched in genes in synaptic signaling pathways and brain-expressed genes, particularly those with high specificity of expression in neurons of the prefrontal cortex and hippocampus. Significant signal enrichment was found in genes encoding targets of antipsychotics, calcium channel blockers, antiepileptics and anesthetics. Integrating expression quantitative trait locus data implicated 15 genes robustly linked to bipolar disorder via gene expression, encoding druggable targets such as HTR6, MCHR1, DCLK3 and FURIN. Analyses of bipolar disorder subtypes indicated high but imperfect genetic correlation between bipolar disorder type I and II and identified additional associated loci. Together, these results advance our understanding of the biological etiology of bipolar disorder, identify novel therapeutic leads and prioritize genes for functional follow-up studies. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.

Study question: What are the European trends and developments in ART and IUI in 2014 as compared to previous years? Summary answer: The 18th ESHRE report on ART shows a continuing expansion of both treatment numbers in Europe and more variability in treatment modalities resulting in a rising contribution to the birth rates in most participating countries. What is known already: Since 1997, ART data generated by national registries have been collected, analysed by the European IVF-monitoring (EIM) Consortium and reported in 17 manuscripts published in Human Reproduction. Study design, size, duration: Continuous collection of European data by the EIM for ESHRE. The data for treatments performed in 2014 between 1 January and 31 December in 39 European countries were provided by national registries or on a voluntary basis by clinics or professional societies. Participants/materials, setting, methods: From 39 countries and 1279 institutions offering ART services, a total of 776 556 treatment cycles, involving 146 148 with IVF, 362 285 with ICSI, 192 027 with frozen embryo replacement (FER), 15 894 with PGT, 56 516 with egg donation (ED), 292 with IVM and 3404 with frozen oocyte replacement (FOR) were reported. European data on IUI using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1364 institutions offering IUI in 26 countries and 21 countries, respectively. A total of 120 789 treatments with IUI-H and 49 163 treatments with IUI-D were included. Main results and the role of chance: In 14 countries (17 in 2013), where all institutions contributed to their respective national registers, a total of 291 235 treatment cycles were performed in a population of ~208 million inhabitants, corresponding to 1925 cycles per million inhabitants (range: 423-2978 per million inhabitants). After treatment with IVF the clinical pregnancy rates (PR) per aspiration and per transfer were marginally higher in 2014 than in 2013, at 29.9 and 35.8% versus 29.6 and 34.5%, respectively. After treatment with ICSI the PR per aspiration and per transfer were also higher than those achieved in 2013 (28.4 and 35.0% versus 27.8 and 32.9%, respectively). After FER with own embryos the PR continued to rise, from 27.0% in 2013 to 27.6% in 2014. After ED a similar trend was observed with PR reaching 50.3% per fresh transfer (49.8% in 2013) and 48.7% for FOR (46.4% in 2013). The delivery rates (DR) after IUI remained stable at 8.5% after IUI-H (8.6% in 2013) and at 11.6% after IUI-D (11.1% in 2013). In IVF and ICSI together, 1, 2, 3 and ≥4 embryos were transferred in 34.9, 54.5, 9.9 and in 0.7% of all treatments, respectively (corresponding to 31.4%, 56.3, 11.5% and 1% in 2013). This evolution in embryo transfer strategy in both IVF and ICSI resulted in a singleton, twin and triplet DR of 82.5, 17.0 and 0.5%, respectively (compared to 82.0, 17.5 and 0.5%, respectively, in 2013). Treatments with FER in 2014 resulted in a twin and triplet DR of 12.4 and 0.3%, respectively (versus 12.5 and 0.3% in 2013). Twin and triplet DR after IUI were 9.5 and 0.3%, respectively, after IUI-H (in 2013:9.5 and 0.6%) and 7.7 and 0.3% after IUI-D (in 2013: 7.5 and 0.3%). Limitation, reasons for caution: The method of data collection and reporting varies among European countries. The EIM receives aggregated data from various countries with variable levels of completeness. Registries from a number of countries have failed to provide adequate data about the number of initiated cycles and deliveries. As long as incomplete data are provided, the results should be interpreted with caution. Wider implications of the findings: The 18th ESHRE report on ART shows a continuing expansion of treatment numbers in Europe. The number of treatments reported, the variability in treatment modalities and the rising contribution to the birth rates in most participating countries point towards the increasing impact of ART on reproduction in Europe. Being the largest data collection on ART, the report gives detailed information about ongoing developments in the field. Study funding/competing interest(s): The study has no external funding and all costs are covered by ESHRE. There are no competing interests.

Elemental iron and manganese powders were blended to form mixtures containing 25, 30 and 35wt.% Mn. Mixtures were compressed into prismatic bars and sintered. Some of the bars were repressed and resintered. Compared to a bar pressed and sintered once, the bar pressed and sintered twice possessed a higher relative density, a higher bending stiffness, and a grid microindentation data set with a lower variance. Bars were immersed in Hank's solution for eight weeks. After this procedure, the bending stiffness were found reduced for all bars except for those pressed, sintered and only repressed, the bending stiffness of which remained unchanged. The repressing has most likely closed up throats connecting the clusters of pores with the free surface of a bar, reducing thus a surface area exposed to a corrosive attack. The resintering has opened up those throats, the electrolyte could fill accessible pores and corrosion weakened the near-surface material, reducing thus a bar's bending stiffness.

STUDY QUESTION Are there any changes in the treatments involving ART and IUI initiated in Europe during 2013 compared with previous years? SUMMARY ANSWER An increase in the overall number of ART cycles resulting from a higher number of countries reporting data was evident, the pregnancy rates (PRs) in 2013 remained stable compared with those reported in 2012, the number of transfers with multiple embryos (3+) was lower than ever before yet the multiple delivery rates (DRs) remained unchanged, and IUI activity and success rates were similar to those of last years. WHAT IS KNOWN ALREADY Since 1997, ART data in Europe have been collected and reported in 16 manuscripts, published in Human Reproduction. STUDY DESIGN, SIZE, DURATION Retrospective data collection of European ART data by the European IVF-monitoring Consortium for ESHRE. Data for cycles between 1 January and 31 December 2013 were collected from National Registers, when existing, or on a voluntary basis by personal information. PARTICIPANTS/MATERIALS, SETTINGS, METHODS From 38 countries (+4 compared with 2012), 1169 clinics reported 686 271 treatment cycles including 144 299 of IVF, 330 367 of ICSI, 154 712 of frozen embryo replacement (FER), 40 244 of egg donation (ED), 247 of IVM, 9791 of PGD/PGS and 6611 of frozen oocyte replacements. European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1095 IUI labs in 22 countries. A total of 175 467 IUI-H and 43 785 IUI-D cycles were included. MAIN RESULTS AND THE ROLE OF CHANCE In 17 countries where all clinics reported to their ART register, a total of 374 177 ART cycles were performed in a population of around 310 million inhabitants, corresponding to 1175 cycles per million inhabitants (range, 235-2703 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.6% (29.4% in 2012) and 34.5% (33.8% in 2012), respectively. For ICSI, the corresponding rates also were stable with 27.8% (27.8% in 2012) and 32.9% (32.3% in 2012). In FER-cycles, the PR per thawing/warming increased to 27.0% (23.1% in 2012). In ED cycles, the PR per fresh transfer increased to 49.8% (48.4% in 2012), to 38.5% (35.9% in 2012) per thawed transfer, and to 46.4% for transfers after FOR (45.1% in 2012). The DRs after IUI remained stable at 8.6% (8.5% in 2012) after IUI-H and was slightly lower after IUI-D (11.1% versus 12.0% in 2012). In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 31.4, 56.3, 11.5, and 1.0% of the cycles, respectively (corresponding numbers were 30.2, 55.4, 13.3 and 1.1% in 2012). The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82., 17.5 and 0.5%, respectively, resulting in a total multiple DR of 18.0% compared to 17.9% in 2012. In FER-cycles, the multiple DR was 12.8% (12.5% twins and 0.3% triplets), nearly the same as in 2012 (12.5, 12.2 and 0.3% respectively). Twin and triplet DRs associated with IUI cycles were 9.5%/0.6% and 7.5%/0.3%, following treatment with husband/donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, the results should be interpreted with caution. WIDER IMPLICATIONS OF THE FINDINGS The 17th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 685 000 cycles reported in 2013 and an increasing contribution to birth rate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies, remains manifest. STUDY FUNDING/COMPETING INTEREST(S) The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

© The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited., Study question: How has the performance of the European regional register of the European IVF-monitoring Consortium (EIM)/European Society of Human Reproduction and Embryology (ESHRE) evolved from 1997 to 2016, as compared to the register of the Centres for Disease Control and Prevention (CDC) of the USA and the Australia and New Zealand Assisted Reproduction Database (ANZARD)? Summary answer: It was found that coherent and analogous changes are recorded in the three regional registers over time, with a different intensity and pace, that new technologies are taken up with considerable delay and that incidental complications and adverse events are only recorded sporadically. What is known already: European data on ART have been collected since 1997 by EIM. Data collection on ART in Europe is particularly difficult due to its fragmented political and legal landscape. In 1997, approximately 78.1% of all known institutions offering ART services in 23 European countries submitted data and in 2016 this number rose to 91.8% in 40 countries. Study design, size, duration: We compared the changes in European ART data as published in the EIM reports (2001-2020) with those of the USA, as published by CDC, and with those of Australia and New Zealand, as published by ANZARD. Participants/materials, setting, methods: We performed a retrospective analysis of the published EIM data sets spanning the 20 years observance period from 1997 to 2016, together with the published data sets of the USA as well as of Australia and New Zealand. By comparing the data sets in these three large registers, we analysed differences in the completeness of the recordings together with differences in the time intervals on the occurrence of important trends in each of them. Effects of suspected over- and under-reporting were also compared between the three registers. X2 log-rank analysis was used to assess differences in the data sets. Main results and the role of chance: During the period 1997-2016, the numbers of recorded ART treatments increased considerably (5.3-fold in Europe, 4.6-fold in the USA, 3.0-fold in Australia and New Zealand), while the number of registered treatment modalities rose from 3 to 7 in Europe, from 4 to 10 in the USA and from 5 to 8 in Australia and New Zealand, as published by EIM, CDC and ANZARD, respectively. The uptake of new treatment modalities over time has been very different in the three registers. There is a considerable degree of underreporting of the number of initiated treatment cycles in Europe. The relationship between IVF and ICSI and between fresh and thawing cycles evolved similarly in the three geographical areas. The freeze-all strategy is increasingly being adopted by all areas, but in Europe with much delay. Fewer cycles with the transfer of two or more embryos were reported in all three geographical areas. The delivery rate per embryo transfer in thawing cycles bypassed that in fresh cycles in the USA in 2012, in Australia and New Zealand in 2013, but not yet in Europe. As a result of these changing approaches, fewer multiple deliveries have been reported. Since 2012, the most documented adverse event of ART in all three registers has been premature birth (

STUDY QUESTION How are ART and IUI regulated, funded and registered in European countries? SUMMARY ANSWER Of the 43 countries performing ART and IUI in Europe, and participating in the survey, specific legislation exists in only 39 countries, public funding (also available in the 39 countries) varies across and sometimes within countries and national registries are in place in 31 countries. WHAT IS KNOWN ALREADY Some information devoted to particular aspects of accessibility to ART and IUI is available, but most is fragmentary or out-dated. Annual reports from the European IVF-Monitoring (EIM) Consortium for ESHRE clearly mirror different approaches in European countries regarding accessibility to and efficacy of those techniques. STUDY DESIGN, SIZE, DURATION A survey was designed using the online SurveyMonkey tool consisting of 55 questions concerning three domains—legal, funding and registry. Answers refer to the countries’ situation on 31 December 2018. PARTICIPANTS/MATERIALS, SETTINGS, METHODS All members of EIM plus representatives of countries not yet members of the Consortium were invited to participate. Answers received were checked, and initial responders were asked to address unclear answers and to provide any additional information they considered important. Tables of individual countries resulting from the consolidated data were then sent to members of the Committee of National Representatives of ESHRE, asking for a second check. Conflicting information was clarified by direct contact. MAIN RESULTS AND THE ROLE OF CHANCE Information was received from 43 out of the 44 European countries where ART and IUI are performed. Thirty-nine countries reported specific legislation on ART, and artificial insemination was considered an ART technique in 35 of them. Accessibility is limited to infertile couples in 11 of the 43 countries. A total of 30 countries offer treatments to single women and 18 to female couples. In five countries ART and IUI are permitted for treatment of all patient groups, being infertile couples, single women and same sex couples, male and female. Use of donated sperm is allowed in 41 countries, egg donation in 38, the simultaneous donation of sperm and egg in 32 and embryo donation in 29. Preimplantation genetic testing (PGT) for monogenic disorders or structural rearrangements is not allowed in two countries, and PGT for aneuploidy is not allowed in 11; surrogacy is accepted in 16 countries. With the exception of marital/sexual situation, female age is the most frequently reported limiting criteria for legal access to ART—minimal age is usually set at 18 years and maximum ranging from 45 to 51 years with some countries not using numeric definition. Male maximum age is set in very few countries. Where permitted, age is frequently a limiting criterion for third-party donors (male maximum age 35 to 55 years; female maximum age 34 to 38 years). Other legal constraints in third-party donation are the number of children born from the same donor (in some countries, number of families with children from the same donor) and, in 10 countries, a maximum number of egg donations. How countries deal with the anonymity is diverse—strict anonymity, anonymity just for the recipients (not for children when reaching legal adulthood age), mixed system (anonymous and non-anonymous donations) and strict non-anonymity. Public funding systems are extremely variable. Four countries provide no financial assistance to patients. Limits to the provision of funding are defined in all the others i.e. age (female maximum age is the most used), existence of previous children, maximum number of treatments publicly supported and techniques not entitled for funding. In a few countries, reimbursement is linked to a clinical policy. The definition of the type of expenses covered within an IVF/ICSI cycle, up to what limit and the proportion of out-of-pocket costs for patients is also extremely dissimilar. National registries of ART and IUI are in place in 31 out of the 43 countries contributing to the survey, and a registry of donors exists in 18 of them. LIMITATIONS, REASONS FOR CAUTION The responses were provided by well-informed and committed individuals and submitted to double checking. Since no formal validation was in place, possible inaccuracies cannot be excluded. Also, results are a cross section in time and ART and IUI legislations within European countries undergo continuous evolution. Finally, several domains of ART activity were deliberately left out of the scope of this ESHRE survey. WIDER IMPLICATIONS OF THE FINDINGS Results of this survey offer a detailed view of the ART and IUI situation in European countries. It provides updated and extensive answers to many relevant questions related to ART usage at national level and could be used by institutions and policymakers in planning services at both national and European levels. Study funding/competing interest(s) The study has no external funding, and all costs were covered by ESHRE. There were no competing interests. ESHRE Pages are not externally peer reviewed. This article has been approved by the Executive Committee of ESHRE.

Study question What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? Summary answer In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. What is known already Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. Study design, size, duration Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. Participants/materials, setting, methods Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. Main results and the role of chance The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). Limitations, reasons for caution The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. Wider implications of the findings This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. Study funding/competing interest This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. Trial registration number None.

Negative symptoms are highly relevant in the long-term course of schizophrenia and are an important target domain for the development of novel interventions. Recently, transcranial direct current stimulation (tDCS) of the prefrontal cortex has been investigated as a treatment option in schizophrenia. In this proof-of-concept study, 20 schizophrenia patients with predominantly negative symptoms were randomized to either 10 sessions of add-on active (2 mA, 20min) or sham tDCS (anode: left DLPFC/F3; cathode: right supraorbital/F4). Primary outcome measure was the change in the Scale for the Assessment of Negative Symptoms (SANS) sum score; secondary outcomes included reduction in Positive and Negative Syndrome Scale (PANSS) scores and improvement of depressive symptoms, cognitive processing speed, and executive functioning. Sixteen patients underwent 4 functional connectivity magnetic resonance imaging (fcMRI) scans (pre and post 1st and pre and post 10th tDCS) to investigate changes in resting state network connectivity after tDCS. Per-protocol analysis showed a significantly greater decrease in SANS score after active (−36.1%) than after sham tDCS (−0.7%). PANSS sum scores decreased significantly more with active (−23.4%) than with sham stimulation (−2.2%). Explorative analysis of fcMRI data indicated changes in subgenual cortex and dorsolateral prefrontal cortex (DLPFC) connectivity within frontal-thalamic-temporo-parietal networks. The results of this first proof-of-concept study indicate that prefrontal tDCS may be a promising intervention for treatment of schizophrenia with predominant negative symptoms. Large-scale randomized controlled studies are needed to further establish prefrontal tDCS as novel treatment for negative symptoms in schizophrenia.

Premenopausal women undergoing chemotherapy are at high risk for premature ovarian failure and its long-term consequences. Data on potential markers to evaluate ovarian reserve pre- and posttreatment are limited. Anti-Müllerian hormone (AMH) known for ovarian reserve in reproductive medicine could be a surrogate marker and was assessed in premenopausal breast cancer patients of the SUCCESS A study (EUDRA-CT no. 2005-000490-21).We identified 170 premenopausal patients, age ≤ 40 years at trial entry, who received FEC-Doc as taxane-anthracylince based chemotherapy. Blood samples were taken at three time points: Before, four weeks after and two years after adjuvant chemotherapy. Serum AMH-levels were evaluated in a central laboratory by a quantitative immunoassay AMH Gen II ELISA (Beckman Coulter, Brea, USA).Median age was 36 years (21-40 years). Median serum AMH-level before chemotherapy was 1.37 ng/ml (range 0.1-11.3 ng/ml). Four weeks after chemotherapy AMH-levels dropped in 98.6% of the patients to0.1 ng/ml (range 0.1-0.21 ng/ml). After two years, 73.3% (n = 101) showed no evidence of ovarian function recovery (AMH0.1 ng/ml, range 0.1-3.9 ng/ml). Permanent chemotherapy induced amenorrhea occurred only in 50.6% of the patients.In this analysis, premenopausal patients showed a high rate of ovarian impairment reflected by low AMH-levels after chemotherapy.

Study Question The 16th European IVF-monitoring (EIM) report presents the data of the treatments involving assisted reproductive technology (ART) and intrauterine insemination (IUI) initiated in Europe during 2012: are there any changes compared with previous years? Summary Answer Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year, the pregnancy rates (PRs) in 2012 remained stable compared with those reported in 2011, and the number of transfers with multiple embryos (3+) and the multiple delivery rates were lower than ever before. What is Known Already Since 1997, ART data in Europe have been collected and re-ported in 15 manuscripts, published in Human Reproduction. Study Design, Size, Duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE). Data for cycles between 1 January and 31 December 2012 were collected from National Registers, when existing, or on a voluntary basis by personal information. Participants/Materials, Setting, Methods From 34 countries (+1 compared with 2011), 1111 clinics reported 640 144 treatment cycles including 139 978 of IVF, 312 600 of ICSI, 139 558 of frozen embryo replacement (FER), 33 605 of egg donation (ED), 421 of in vitro maturation, 8433 of preimplantation genetic diagnosis/preimplantation genetic screening and 5549 of frozen oocyte replacements (FOR). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 1126 IUI labs in 24 countries. A total of 175 028 IUI-H and 43 497 IUI-D cycles were included. Main Results and the Role of Chance In 18 countries where all clinics reported to their ART register, a total of 369 081 ART cycles were performed in a population of around 295 million inhabitants, corresponding to 1252 cycles per million inhabitants (range 325-2732 cycles per million inhabitants). For all IVF cycles, the clinical PRs per aspiration and per transfer were stable with 29.4 (29.1% in 2011) and 33.8% (33.2% in 2011), respectively. For ICSI, the corresponding rates also were stable with 27.8 (27.9% in 2011) and 32.3% (31.8% in 2011). In FER cycles, the PR per thawing/warming increased to 23.1% (21.3% in 2011). In ED cycles, the PR per fresh transfer increased to 48.4% (45.8% in 2011) and to 35.9% (33.6% in 2011) per thawed transfer, while it was 45.1% for transfers after FOR. The delivery rate after IUI remained stable, at 8.5% (8.3% in 2011) after IUI-H and 12.0% (12.2% in 2011) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 30.2, 55.4, 13.3 and 1.1% of the cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 82.1, 17.3 and 0.6%, respectively, resulting in a total multiple delivery rate of 17.9% compared with 19.2% in 2011 and 20.6% in 2010. In FER cycles, the multiple delivery rate was 12.5% (12.2% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.0%/0.4% and 7.2%/0.5%, following treatment with husband and donor semen, respectively. LIMITATIONS, REASONS FOR CAUTION The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider Implications of the Findings The 16th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 640 000 cycles reported in 2012 with an increasing contribution to birthrate in many countries. However, the need to improve and standardize the national registries, and to establish validation methodologies remains manifest. STUDY FUNDING/COMPETING INTERESTS The study has no external funding; all costs are covered by ESHRE. There are no competing interests.

BACKGROUND This 11th European IVF-monitoring report presents the results of assisted reproductive technology (ART) treatments initiated in Europe during 2007. METHODS From 33 countries, 1029 clinics reported 493 184 treatment cycles: IVF (120 761), ICSI (256 642), frozen embryo replacement (91 145), egg donation (15 731), preimplantation genetic diagnosis/preimplantation genetic screening (4638), in vitro maturation (660) and frozen oocytes replacements (3607). Overall, this represents a 7.6% increase since 2006, mostly related to an increase in all registers. IUI using husband/partner's (IUI-H) and donor (IUI-D) semen was reported from 23 countries: 142 609 IUI-H (+6.2%) and 26 088 IUI-D (+7.2%). RESULTS In 18 countries where all clinics reported, 376 971 ART cycles were performed in a population of 425.6million (886 cycles per million). The clinical pregnancy rates per aspiration and per transfer were 29.1 and 32.8% for IVF, and 28.6 and 33.0% for ICSI. Delivery rate after IUI-H was 10.2% in women aged < 40 years. In IVF/ICSI cycles, 1, 2, 3 and ≥4 embryos were transferred in 21.4, 53.4, 22.7 and 2.5% of cycles, with no decline in the number of embryos per transfer since 2006. The proportion of multiple deliveries (22.3: 21.3% twin and 1.0% triplet), did not decrease compared with 2006 (20.8%) and 2005 (21.8%). In women < 40 years undergoing IUI-H, twin deliveries occurred in 11.7% and triplets in 0.5%. CONCLUSIONS In comparison with previous years, the reported number of ART cycles in Europe increased in 2007; pregnancy rates increased marginally, but the earlier decline in the number of embryos transferred and multiple births did not continue.

Background: Premenopausal women undergoing chemotherapy are at risk of premature ovarian failure and long term side-effects caused by premature menopause. However, knowledge about the rate of ovarian failure and potential markers to evaluate the ovarian reserve is limited, especially in the context of modern chemotherapy concepts. Therefore, Anti-Müllerian hormone (AMH) was measured at before, immediately after and 2 years after chemotherapy in premenopausal patients of the SUCCESS study. Materials and Methods: The German SUCCESS trial is a multicenter phase III study comparing FEC-Docetaxel vs. FEC-Docetaxel+Gemcitabine as adjuvant treatment in patients with node positive or high risk node negative primary breast cancer. Blood samples were taken prior to and 4 weeks after last cycle of adjuvant chemotherapy, as well as after 2 years of follow up. We retrospecitvely identified 170 patients stratified premenopausal and aged 40 years or younger at trial entry, who received 3cycles of FEC (500/100/500mg/m2) q3w followed by 3 cycles of docetaxel (100mg/m2) q3w as one of the most commonly used chemotherapy regimens in Europe. Serum AMH levels were evaluated in a central laboratory by a manual immunoassay AMH DSL ELISA (Diagnostic Systems Laboratories, Webster, USA). Results: Median age within this subgroup was 36 years (21-40 years). 48% of the patients had a tumor stage pT1 and 54% were node positive. 69% were hormone receptor positive and 29% Her2 positive. Median serum AMH level before adjuvant chemotherapy was 1.32 ng/ml (range Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-14-05.

The paper aimed at the water vapour induced corrosion of the Fe–40 at.% Al alloy under applied constant loads using tensile apparatus. To interpret the registered experimental curves they were converted in accordance with Ternes method. Microfractographic investigations were conducted on specimens after cracking. Results reveal susceptibility of the iron aluminide to stress corrosion, and influence of heat treatment on this process.

Cellular materials from hollow bronze spheres were prepared and investigated. The main aim was to determine the effective Young’s modulus of cellular materials by means of the dynamic resonant method, and the next goal was to demonstrate the possibility of using sandwich samples for such determination. For this purpose, two kinds of samples were prepared: quasihomogeneous rods consisting entirely of a cellular material, and sandwich rods containing the cellular material only in a core. Resonant frequencies of the fundamental flexural modes of all these samples were measured, and corresponding flexural rigidities were evaluated. Obtained values of flexural rigidities were subsequently utilized for calculation of the effective Young’s modulus of cellular material. A reasonable agreement between the modulus values determined by means of quasihomogeneous and sandwich samples was obtained. This indicates that the sandwich samples could be used for measuring the material properties of particular layers.

Literature One prominent symptom in addiction disorders is the strong desire to consume a particular substance or to display a certain behaviour (craving). Especially the strong association between craving and the probability of relapse emphasises the importance of craving in the therapeutic process. Neuroimaging studies have shown that craving is associated with increased responses, predominantly in fronto-striatal areas. Aim and Methods The aim of the present study is the modification of craving-related neuronal responses in patients with alcohol addiction using fMRI real-time neurofeedback. For that purpose, patients with alcohol use disorder and healthy controls participated once in neurofeedback training; during the sessions neuronal activity within an individualized cortical region of interest (ROI) (anterior cingulate cortex, insula, dorsolateral prefrontal cortex) was evaluated. In addition, variations regarding the connectivity between brain regions were assessed in the resting state. Results and Discussion The results showed a significant reduction of neuronal activity in patients at the end of the training compared to the beginning, especially in the anterior cingulate cortex, the insula, the inferior temporal gyrus and the medial frontal gyrus. Furthermore, the results show that patients were able to regulate their neuronal activities in the ROI, whereas healthy subjects achieved no significant reduction. However, there was a wide variability regarding the effects of the training within the group of patients. After the neurofeedback-sessions, individual craving was slightly reduced compared to baseline. The results demonstrate that it seems feasible for patients with alcohol dependency to reduce their neuronal activity using rtfMRI neurofeedback. In addition, there is some evidence that craving can be influenced with the help of this technique. Future Prospects In future, real-time fMRI might be a complementary neurophysiological-based strategy for the psychotherapy of patients with psychiatric or psychosomatic diseases. For that purpose, the stability of this effect and the generalizability needs to be assessed.

Rectangular-bar specimens with nonhomogeneous (quasilayered) porosity distribution were prepared from an iron powder. Using these specimens, differences were observed in effective Young's modulus values determined experimentally by means of specimen flexural vibrations with bending in the plane of quasilayers and in the plane perpendicular to quasilayers. To account for these differences, general expressions for resonance frequencies of flexural vibrations of model quasilayered bars were derived in a theoretical way. The model quasilayered bar means a prismatic bar of rectangular cross section, with material Young's modulus varying continuously only along one of transverse directions. Substituting theoretical resonance frequencies, instead of experimentally measured ones, into the routine evaluation procedure of the dynamical resonant method, theoretical values of effective Young's modulus were calculated. In majority of theoretically investigated simple model examples with lowered modulus of surface regions the effective modulus determined by means of the frequency of sample flexural vibration perpendicular to layers is lower than the effective modulus determined by means of the vibration parallel to the layers. These theoretical results explain qualitatively the effective modulus differences obtained for our quasilayered samples in an experimental way.

Introduction Transcranial direct current stimulation (tDCS) is currently investigated for the treatmentof various neuropsychiatric disorders. Neuroplastic effects may be achieved by prolonged neuronal depolarization/hyperpolarization. Objectives Schizophrenia studies revealed a neuroplasticity deficit of cortical areas. Promising results of anodal/cathodal tDCS for acute and chronic symptoms were shown in one randomized clinical trial and several case reports. Aims To improve negative symptoms, anodal tDCS over the left dorsolateral prefrontal cortex (DLPFC) and cathodal tDCS above the supraorbital region was used. Clinical scores were assessed with Positive and Negative Symptoms Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS). Methods 20 patients with predominant negative symptoms and stable medication (>3 weeks) were randomized to active or sham group. Anode was placed over the left DLPFC, cathode over right orbit. 2 mA tDCS was delivered 10 times within weeks 1 and 2. Concomitant medication was continued. Functional connectivity MRI (fcMRI) was performed before and after tDCS. Results Post-hoc test (least significant difference, factor ‘group’) showed significant PANSS amelioration in the active group (p = 0.014) for the follow-up, two weeks after the end of stimulation. SANS revealed significant improvement in the active group in week 1 (p = 0.047), week 2 (p = 0.005), and follow-up (p = 0.011). In the active group, fcMRI showed a significant deactivated cluster (corrected p Conclusions tDCS is a promising tool to improve various schizophrenic symptoms that are otherwise often difficult to treat.

Study question The 13th European in vitro fertilization (IVF)-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2009: are there any changes in the trends compared with previous years? Summary answer Despite some fluctuations in the number of countries reporting data, the overall number of ART cycles has continued to increase year by year and, while pregnancy rates in 2009 remained similar to those reported in 2008, the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. What is known already Since 1997, ART data in Europe have been collected and reported in 12 manuscripts, published in Human Reproduction. Study design, size, duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1st January and 31st December are collected on a yearly basis; the data are collected by the National Registers, when existing, or on a voluntary basis. Participants/materials setting, methods From 34 countries (-2 compared with 2008), 1005 clinics reported 537 463 treatment cycles including: IVF (135 621), intracytoplasmic sperm injection (ICSI, 266 084), frozen embryo replacement (FER, 104 153), egg donation (ED, 21 604), in vitro maturation (IVM, 1334), preimplantation genetic diagnosis/screening (PGD/PGS, 4389) and frozen oocyte replacements (FOR, 4278). European data on intrauterine insemination using husband/partner's semen (IUI-H) and donor (IUI-D) semen were reported from 21 and 18 countries, respectively. A total of 162 843 IUI-H (+12.7%) and 29 235 IUI-D (+17.3%) cycles were included. Data available from each country are presented in the tables; total values (as numbers and percentages) refer to those countries where all data have been reported. Main results and the role of chance In 21 countries where all clinics reported to the ART register, a total of 399 020 ART cycles were performed in a population of 373.8 million, corresponding to 1067 cycles per million inhabitants. For IVF, the clinical pregnancy rates per aspiration and per transfer were 28.9 and 32.9%, respectively and for ICSI, the corresponding rates were 28.7 and 32.0%. In FER cycles, the pregnancy rate per thawing was 20.9%; in ED cycles, the pregnancy rate per transfer was 42.3%. The delivery rate after IUI-H was 8.3 and 13.4% after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 24.2, 57.7, 16.9 and 1.2%, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (combined) were 79.8, 19.4 and 0.8%, respectively, resulting in a total multiple delivery rate of 20.2%, compared with 21.7% in 2008, 22.3% in 2007, 20.8% in 2006 and 21.8% in 2005. In FER cycles, the multiple delivery rate was 13.0% (12.7% twins and 0.3% triplets). Twin and triplet delivery rates associated with IUI cycles were 10.4/0.7% and 10.3/0.5%, following treatment with husband and donor semen, respectively. Limitations, reasons for caution The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider implications of the findings The 13th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than half a million of cycles reported in 2009. The use of ICSI has reached a plateau. Pregnancy and delivery rates after IVF and ICSI remained relatively stable compared with 2008 and 2007. The number of multiple embryo transfers (3+ embryos) and the multiple delivery rate have shown a clear decline.

Study question The 15th European IVF-monitoring (EIM) report presents the results of treatments involving assisted reproductive technology (ART) initiated in Europe during 2011: are there any changes in the trends compared with previous years? Summary answer Despite some fluctuations in the number of countries reporting data, while the overall number of ART cycles has continued to increase year by year, the pregnancy rates in 2011 decreased slightly to those reported in 2010, and the number of transfers with multiple embryos (3+) and the multiple delivery rates declined. What is known already Since 1997, ART data in Europe have been collected and reported in 14 manuscripts, published in Human Reproduction. Study design, size, duration Retrospective data collection of European ART data by the EIM Consortium for the European Society of Human Reproduction and Embryology (ESHRE); cycles started between 1 January and 31 December 2011 are collected on a yearly basis. The data are collected by National Registers, when existing, or on a voluntary basis by personal information. Participants/materials setting, methods From 33 countries (+2 compared with 2010), 1064 clinics reported 609 973 treatment cycles including: IVF 138 592, ICSI 298 918, frozen embryo replacement (FER) 129 693, egg donation (ED) 30 198, in vitro maturation 511, preimplantation genetic diagnosis/screening 6824 and frozen oocyte replacements 5237. European data on intrauterine insemination (IUI) using husband/partner's semen (IUI-H) and donor semen (IUI-D) were reported from 861 IUI laboratories in 24 countries. A total of 174 390 IUI-H and 41 151 IUI-D cycles were included. Main results and the role of chance In 17 countries where all clinics reported to the ART register, a total of 361 972 ART cycles were performed in a population of 285 million inhabitants, corresponding to 1269 cycles per million inhabitants. For all IVF cycles, the clinical pregnancy rates per aspiration and per transfer were stable with 29.1 and 33.2%, respectively, and for ICSI, the corresponding rates also were stable with 27.9 and 31.8%, respectively. In FER cycles, the pregnancy rate per thawing increased to 21.3% if compared with previous years. In ED cycles, the pregnancy rate per fresh transfer decreased to 45.8% (47.4% in 2010) and increased to 33.6% (33.3% in 2010) per thawed transfer. The delivery rate after IUI-H decreased to 8.3 (8.9 in 2010), and to 12.2% (13.8% in 2010) after IUI-D. In IVF and ICSI cycles, 1, 2, 3 and 4+ embryos were transferred in 27.5, 56.7, 14.5 and 1.3% of cycles, respectively. The proportions of singleton, twin and triplet deliveries after IVF and ICSI (added together) were 80.8, 18.6 and 0.6%, respectively, resulting in a total multiple delivery rate of 19.2% compared with 20.6% in 2010, 20.2% in 2009, 21.7% in 2008, 22.3% in 2007 and 20.8% in 2006. In FER cycles, the multiple delivery rate was 13.2% (12.8% twins and 0.4% triplets). Twin and triplet delivery rates associated with IUI cycles were 9.7/0.6% and 7.3/0.3%, following IUI-H and IUI-D treatment, respectively. Limitations, reasons for caution The method of reporting varies among countries, and registers from a number of countries have been unable to provide some of the relevant data such as initiated cycles and deliveries. As long as data are incomplete and generated through different methods of collection, results should be interpreted with caution. Wider implications of the findings The 15th ESHRE report on ART shows a continuing expansion of the number of treatment cycles in Europe, with more than 600 000 cycles reported in 2011. Since 2006, the proportion of IVF to ICSI cycles has reached a plateau after a small decrease in 2009. Pregnancy and delivery rates after IVF remained relatively stable compared with 2010 and 2009. The pregnancy rate per aspiration in ICSI cycles declined for the first time by 0.9%. The multiple delivery rate is lower than ever before. Study funding/competing interests The study had no external funding; all costs are covered by ESHRE. There are no competing interests.

The constraints to the effective electrical conductivity were derived as function of distribution of material electrical conductivity throughout the sample. If the sample consists only of homogeneous isotropic matrix and pores, the constraints to effective electrical conductivity take the form very similar to the constraints derived previously for the effective Young’s modulus of porous materials. The differences occurring in expressions are due to the fact that elastic properties of an isotropic matrix material are characterized by two quantities, e.g. Young’s modulus and Poisson’s ratio, while the conductivity is characterized only by one quantity. But regardless of the small differences, in the both cases the key role in determining the properties is played by the minimum load-bearing cross section of the sample considered., Zapreke učinkovitoj električnoj provodnosti izvedene su kao funkcije distribucije električne provodnosti i poprimaju oblik vrlo sličan onim smetnjama koje su ranije izvedeni za učinkovit Youngov modul poroznog materijala. Razlike koje se pojavljuju u izrazima nastale su zbog činjenice da su svojstva elastičnosti nekog izotropnog matričnog materijala okarakterizirane dvjema količinama, npr. Youngovim modulom i Poissonovim odnosom, dok je provodnost okarakterizirana samo jednom količinom, ali bez obzira na male razlike, u obadva ta slučaja ključnu ulogu u određivanju svojstva igra primjer uzorka pod minimalnim naponom.

Rectangular bar-shaped sandwich-like samples consisting of a cellular-material core between two standard material layers were prepared. The cellular materials were made of both ferrous and bronze hollow spheres. Using these specimens and testing method based on flexural vibrations, expected differences were observed in effective modulus values determined by means of vibrations parallel and perpendicular to layers. Information on distribution of material throughout the bar cross section was obtained through metallographic studies. The thickness of particular layers, measured values of “parallel” and “perpendicular” effective flexural modulus, and expressions derived for flexural rigidity of quasi-layered bars were used for evaluating the values of effective Young’s modulus of material of particular layers constituting the sample. Reasonable agreement was found among results obtained for various samples., Pripremljeni su pravokutni sendvič-uzorci motki koji se sastoje od jezgre sa staničnim materijalom između dva sloja standardnog materijala. Stanični materijali su napravljeni od željeznih i brončanih šupljih kugli. Uporabom tih uzoraka i metoda testiranja zasnovane na vibracijama savijanja, očekivane razlike su prijećene u postojećim vrijednostima modula određenih pomoću vibracija paralelnih i okomitih na slojeve. Informacija o rasporedu materijala u presjeku motke dobivena je na osnovu proučavanja metalografije. Debljina pojedinih slojeva izmjerenih vrijednosti “paralelnih” i “okomitih” stvarnog modula savijanja i izraza izvedenih iz savitljive krutosti poluslojevnih motki koje se koriste za procjenjivanje vrijednosti stvarnog efektnog Youngovog modula materijala pojedinih slojeva koji sačinjavaju uzorak. Razumno suglasje je pronađeno među rezultatima dobivenim za razne uzorke.

Presented here is the case of a paraneoplastic cerebral degeneration (PCD) in a female patient with breast cancer and the indication of anti-Yo antibodies in the cerebrospinal fluid (CSF) and serum. The patient's primary indications were dizziness and a severe gait ataxia. The indication of anti-Yo antibodies led to the conclusion of the existence of a paraneoplastic cerebral degeneration. The antibodies in question are anti-Purkinje-cell autoantibodies acting against the antigens common to tumor and Purkinje cells which occur in association with a certain percentage of breast or ovarian cancers. The diagnosis of the primary tumor, that is clinically undetectable with conventional imaging processes, is performed with the aid of positron emission tomography (PET) to detect the presence of axillary lymph node metastases. The micro-invasive mammary carcinoma was able to be localized with the aid of MR mammography and, after MR mammography marking, was removed. The patient subsequently received adjuvant treatment with epirubicine and cyclophosphamide. This treatment failed to influence the paraneoplastic neurological symptoms.

The cylindrical and rod-shaped specimens were prepared by gravity sintering from Cu-Sn hollow spheres. On these samples, both static compression tests and measurements of resonance frequencies were performed. The compressive stress-strain curves revealed the features characteristic for a closed-cell ductile cellular solid. The removal of in general open porosity among loosely packed closed metallic hollow spheres was recognized as the principal mode of plastic deformation. The approximative effective moduli of elasticity were determined for cellular materials under consideration by means of the measurements of resonance frequencies on rod-shaped specimens., Cilindrični i šipkasti uzorci su pripremljeni gravitacionim sinterovanjem šupljih Cu-Sn kugli. Na tim uzorcima su provedena ispitivanja statičke kompresije i mjerenja rezonantnih frekvencija. Krivulja naprezanje-rastezanje nam pokazuje svojstva karakteristična za plastične celularne krute materijale sa zatvorenim ćelijama. Uklanjanje uglavnom otvorene povezanosti među labavo povezanim šupljim metalnim kuglama prepoznajemo kao glavni način plastične deformacije. Za celularne materijale koji se razmatraju određeni su približno učinkoviti moduli elastičnosti mjerenjem frekvencija rezonancije na šipkasto oblikovanim uzorcima.

Several previous studies have shown that real-time neurofeedback can be used to willfully regulate neuronal activity in specific brain-regions. The aim of the study was to find out whether patients with alcohol dependency would be able to learn how to regulate their neuronal activity in dependency-associated areas. In addition, neurofeedback-related variations to craving for alcohol are assessed. 11 patients with alcohol dependency and 14 healthy participants were investigated. Neutral and alcohol-associated pictures were presented during functional MRI measurements. Alcohol-associated BOLD-responses in the frontal cortex (anterior cingulate cortex, dorsolateral prefrontal cortex, insula) were used as a region of interest (ROI). During the neurofeedback sessions, participants were instructed to down regulate their neuronal activity in the specific ROI during the presentation of alcohol-associated pictures. The results show that the patients were able to regulate their neuronal activities in areas related to dependency (p=0,048). After the neurofeedback-sessions, the individual craving (valued on the basis of the obsessive compulsive drinking scale) was slightly reduced in comparison to before the sessions (p=0,068). It seems feasible for patients with alcohol dependency to down-regulate their neuronal activity using rtfMRI. In addition, there is some evidence that craving can be influenced by this technique. However, so far, there were great differences within the group of patients.

Background Over the last decade, the study of functional connectivity networks has dramatically expanded across diverse research fields as functional MRI connectivity (fcMRI) or EEG connectivity. The aim of this study was to evaluate functional connectivity in the course of the day using two different imaging methods. Methods 27 healthy subjects (male and female students in the age-range between 18-30 years) underwent 6 repeated fcMRI measurements over 12 hours in a 3T Philips Achieva MR scanner. The subjects were instructed to close their eyes and not to think on anything in particular. Resting State EEG was recorded outside the MR scanner with eyes closed and eyes open using a Brain MR Amplifier with 32 channels. Sleep deprivation was kept constant across subjects and the subjects were restricted to low-calorie food. EEG was analysed for coherence and EEG-phase between all EEg channels in sensor and source space. Results The time course of 20 functional MRI networks were extracted and previous described functional networks were found. Eyes closed and eyes open EEG showed similar and distinct spatial correspondence. We found a good overlap for the Default Mode Network and the Frontal-parietal network. Day of time influenced the EEG measurements partly. Conclusion The findings of fcMRI and EEG connectivity are unique with high spatial resolution for fcMRI and high temporal resolution for EEG. Both measurements methods contribute further to our understanding of complex functional connectivity networks.