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1.
J Neurosci ; 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38830759

RESUMO

Congenital single-sided deafness (SSD) leads to an aural preference syndrome that is characterized by overrepresentation of the hearing ear in the auditory system. Cochlear implantation (CI) of the deaf ear is an effective treatment for SSD. However, the newly introduced auditory input in congenital SSD often does not reach expectations in late-implanted CI recipients with respect to binaural hearing and speech perception. In a previous study, a reduction of interaural time difference (ITD) sensitivity has been shown in unilaterally congenitally deaf cats (uCDC). In the present study, we focused on the interaural level difference (ILD) processing in the primary auditory cortex. The uCDC group was compared with hearing cats (HC) and bilaterally congenitally deaf cats (CDC). The ILD representation was reorganized, replacing the preference for the contralateral ear with a preference for the hearing ear, regardless of the cortical hemisphere. In accordance with the previous study, uCDCs were less sensitive to interaural time differences than HCs, resulting in unmodulated ITD responses, thus lacking directional information. Such incongruent ITDs and ILDs cannot be integrated for binaural sound source localization. In normal hearing the predominant effect of each ear is excitation of auditory cortex in the contralateral cortical hemisphere and inhibition in the ipsilateral hemisphere. In SSD, however, auditory pathways reorganized such that the hearing ear produced greater excitation in both cortical hemispheres and the deaf ear produced weaker excitation and preserved inhibition in both cortical hemispheres.Significance statement Congenital single-sided deafness is a clinically relevant form of hearing loss. We studied this phenomenon in a unique animal model with congenital deafness of one ear and normal hearing of the other ear with electrical stimulation on both ears. Differential effects of single-sided deafness on interaural time and level difference sensitivity were observed, consistent with the aural preference syndrome. The influence of the previously hearing ear became dominant and the deaf ear mildly suppressive in the majority of units in both hemispheres, resulting in an inconsistent representation of binaural cues. These changes in neuronal representation of the two ears explain why late restoration with cochlear implants in single-sided deafness often results in insufficient benefit of the previously deaf ear.

2.
Phys Rev Lett ; 132(12): 123202, 2024 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-38579236

RESUMO

We studied strong-field multiphoton ionization of 1-iodo-2-methylbutane enantiomers with 395 nm circularly polarized laser pulses experimentally and theoretically. For randomly oriented molecules, we observe spin polarization up to about 15%, which is independent of the molecular enantiomer. Our experimental findings are explained theoretically as an intricate interplay between three contributions from HOMO, HOMO-1, and HOMO-2, which are formed of 5p-electrons of the iodine atom. For uniaxially oriented molecules, our theory demonstrates even larger spin polarization. Moreover, we predict a sizable enantiosensitive photoelectron circular dichroism of about 10%, which is different for different spin states of photoelectrons.

3.
Phys Rev Lett ; 132(23): 233002, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38905657

RESUMO

We experimentally study the influence of the binding energy on nondipole effects in K-shell single-photon ionization of atoms at high photon energies. We find that for each ionization event, as expected by momentum conservation, the photon momentum is transferred almost fully to the recoiling ion. The momentum distribution of the electrons becomes asymmetrically deformed along the photon propagation direction with a mean value of 8/(5c)(E_{γ}-I_{P}) confirming an almost 100 year old prediction by Sommerfeld and Schur [Ann. Phys. (N.Y.) 396, 409 (1930)10.1002/andp.19303960402]. The emission direction of the photoions results from competition between the forward-directed photon momentum and the backward-directed recoil imparted by the photoelectron. Which of the two counteracting effects prevails depends on the binding energy of the emitted electron. As an example, we show that at 20 keV photon energy, Ne^{+} and Ar^{+} photoions are pushed backward towards the radiation source, while Kr^{+} photoions are emitted forward along the light propagation direction.

4.
J Intellect Disabil Res ; 67(3): 186-204, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36814136

RESUMO

BACKGROUND: Infants born at extremely low birthweight (ELBW: ≤1000 g) are vulnerable to intellectual disabilities, but the factors that may distinguish between ELBW survivors with and without these impairments are not well understood. In this study, prospective associations between neonatal factors and functional outcomes in childhood and adolescence were compared in ELBW survivors with and without borderline intellectual functioning (BIF). METHODS: Borderline intellectual functioning was defined by IQ < 85, assessed at 8 years. Among 146 ELBW survivors, 48 (33%) had IQ scores under 85, and 98 (67%) had scores equal to or over 85. Group differences in demographic and risk factors were assessed via t-test, chi-squared analysis or non-parametric tests. Neonatal factors that differed between ELBW groups were tested for association with adaptive behaviour assessed at age 5 years, and reading and arithmetic skills assessed at ages 8 and 15 years, using hierarchical regression models. RESULTS: Extremely low birthweight survivors with BIF had significantly lower birthweights than ELBW survivors without BIF (790 vs. 855 g, P < 0.01) and were more likely to be born to mothers with lower socioeconomic status (SES) (78% vs. 48%, P < 0.01). These ELBW survivors also were more likely to be diagnosed with significant neurosensory impairment (NSI; 35% vs. 19%, P < 0.04), experienced more bronchopulmonary dysplasia (56% vs. 38%, P < 0.04), received more days of respiratory support (median 33 vs. 14 days, P < 0.01) and remained in hospital for longer periods (median 81 vs. 63 days, P < 0.03). Birthweight, familial SES, NSI and duration of respiratory support were significant predictors for one or more outcomes. Across groups, lower familial SES was associated with lower academic scores (Ps < 0.05), and NSI predicted lower adaptive functioning (Ps < 0.001). Other associations were moderated by group: among ELBW survivors with BIF, heavier birthweights predicted better arithmetic skills, the presence of NSI was associated with poorer arithmetic skills and more ventilation days predicted poorer reading skills. CONCLUSIONS: At birth, ELBW survivors with BIF faced more physiological and social disadvantages and required more medical intervention than their ELBW peers without BIF. Smaller birth size, NSI burden and prolonged neonatal ventilatory support displayed gradients of risk for childhood and adolescent academic outcomes across groups. Whereas academic performance in ELBW survivors with BIF was sensitive to variation in birth size, NSI or ventilation days, ELBW survivors without BIF attained thresholds of intellectual ability that were sufficient to support higher levels of academic performance at both ages, regardless of their status on these factors. The findings are discussed in relation to Zigler's developmental theory of intellectual disability.


Assuntos
Deficiência Intelectual , Deficiências da Aprendizagem , Recém-Nascido , Lactente , Feminino , Humanos , Adolescente , Pré-Escolar , Criança , Recém-Nascido de Peso Extremamente Baixo ao Nascer , Peso ao Nascer , Sobreviventes , Cognição
5.
Phys Rev Lett ; 128(5): 053001, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35179929

RESUMO

We present the momentum distributions of the nucleus and of the electrons from double ionization of the helium atom by Compton scattering of photons with hν=40 keV. We find that the doubly charged ion momentum distribution is very close to the Compton profile of the nucleus in the ground state of the helium atom, and the momentum distribution of the singly charged ion to give a precise image of the electron Compton profile. To reproduce these results, nonrelativistic calculations require the use of highly correlated initial- and final-state wave functions.

6.
Phys Chem Chem Phys ; 24(44): 27121-27127, 2022 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-36342321

RESUMO

During the last decade, X-ray free-electron lasers (XFELs) have enabled the study of light-matter interaction under extreme conditions. Atoms which are subject to XFEL radiation are charged by a complex interplay of (several subsequent) photoionization events and electronic decay processes within a few femtoseconds. The interaction with molecules is even more intriguing, since intricate nuclear dynamics occur as the molecules start to dissociate during the charge-up process. Here, we demonstrate that by analyzing photoelectron angular emission distributions and kinetic energy release of charge states of ionic molecular fragments, we can obtain a detailed understanding of the charge-up and fragmentation dynamics. Our novel approach allows for gathering such information without the need of complex ab initio modeling. As an example, we provide a detailed view on the processes happening on a femtosecond time scale in oxygen molecules exposed to intense XFEL pulses.

7.
Hum Reprod ; 36(9): 2576-2586, 2021 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-34166497

RESUMO

STUDY QUESTION: Is the rate of fatherhood among men diagnosed with cancer in childhood and early adulthood different from men without cancer, and, if so, have the differences changed over time? SUMMARY ANSWER: Men diagnosed with cancer have had significantly reduced rates of fatherhood compared with undiagnosed men; however, the rates of fatherhood among the cancer survivors have increased markedly over time. WHAT IS KNOWN ALREADY: The number of children and young adolescents who survive cancer has steadily increased over recent decades, with a current 5-year survival rate of approximately 80%. Consequently, life circumstances after cancer have gained increasing importance, including the desire among survivors to have children and a family. ARTs to aid reproduction among cancer survivors have been developed, and fertility preservation is increasingly a topic being discussed before undergoing cancer treatment. But the potential for fertility preservation differs dependent on age at diagnosis and type of cancer. Earlier studies have shown a decreased fertility rate among survivors of child and adolescent cancer compared to those diagnosed in early adulthood. STUDY DESIGN, SIZE, DURATION: This study is a national, register-based cohort study. Men diagnosed with cancer in childhood and early adulthood (<30 years of age) were registered in the Danish Cancer Register in 1978-2016 (n = 9353). According to the time of diagnosis, each cancer-diagnosed man was randomly matched with 150 undiagnosed men from the background population within the same birth year. The men were followed until having their first child, death, migration or the end of the study (31 December 2017) in medical registers and socio-demographic population registers. PARTICIPANTS/MATERIALS, SETTING, METHODS: Fatherhood among the boys and young men diagnosed with cancer were compared with the age-matched comparison group in all statistical analyses. Cancer diagnoses were categorised as central nervous system (CNS) cancers, haematological cancers or solid cancers. Analyses were stratified by age at diagnosis (0-9, 10-19, 20-29 years) and time of diagnosis (1978-1989, 1990-1999, 2000-2009, 2010-2016). Death was incorporated as a competing risk in all analyses. MAIN RESULTS AND THE ROLE OF CHANCE: The study population consisted of 9353 boys and young men diagnosed with cancer between 1978 and 2016 and 1 386 493 men in the age-matched comparison group. Those surviving CNS cancer as young men had the lowest hazard ratio (HR) of fatherhood compared with the age-matched comparison group (HR 0.67, 95% CI 0.57-0.79), followed by survivors of haematological cancers (HR 0.90, 95% CI 0.81-1.01), while the highest chance of fatherhood was among survivors of solid cancers (HR 1.16, 95% CI 1.12-1.20) with a slightly increased HR compared with undiagnosed males. The HR of becoming a father increased over time. From the first decade to the last decade 30 years later, the HR of becoming a father increased for solid tumours (HR 0.78, 95% CI 0.73-0.83 to HR 1.08, 95% CI 0.95-1.22), haematological cancers (HR 0.64, 95% CI 0.53-0.79 to HR 0.97, 95% CI 0.73-1.30) and CNS cancers (HR 0.44, 95% CI 0.34-0.57 to HR 0.98, 95% CI 0.49-1.95) compared to the age-matched comparison group. Also, when compared with the age-matched comparison group, men diagnosed with cancer when aged 20-29 years were more likely became fathers over the time of the study (HR 0.80, 95% CI 0.74-0.86 to HR 1.08, 95% CI 0.96-1.22). LIMITATIONS, REASONS FOR CAUTION: The study was based on register data, and information was not available about the men's fertility potential, whether they had a desire to have children and whether it was possible for them to find a partner. Information about fertility preservation, e.g. sperm freezing, could also have provided additional insights. Furthermore, information about diagnosis and ART treatment would have been beneficial. WIDER IMPLICATIONS OF THE FINDINGS: Information and education of male patients diagnosed with cancer about fertility preservation options and their chances to create their own family is crucial. Reassuringly, time trends showed more men with a previous cancer diagnosis becoming fathers in recent years than in earlier years, reflecting that survival and fertility preservation have improved over time. STUDY FUNDING/COMPETING INTEREST(S): R.S. received a PhD grant from the Rosa Ebba Hansen Foundation and from the Health Foundation (J.nr. 15-B-0095). The funding for the establishment of the DANAC II Cohort was obtained from the Rosa Ebba Hansen Foundation. The authors have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Sobreviventes de Câncer , Neoplasias , Adolescente , Adulto , Criança , Estudos de Coortes , Dinamarca/epidemiologia , Humanos , Masculino , Homens , Neoplasias/epidemiologia , Adulto Jovem
8.
Hum Reprod ; 36(12): 3152-3160, 2021 11 18.
Artigo em Inglês | MEDLINE | ID: mdl-34580714

RESUMO

STUDY QUESTION: Is there an increased risk of breast cancer among women after ART treatment including ovarian hormone stimulation? SUMMARY ANSWER: The risk of breast cancer was slightly increased among women after ART treatment compared to age-matched, untreated women in the background population, and the risk was further increased among women initiating ART treatment when aged 40+ years. WHAT IS KNOWN ALREADY: The majority of breast cancer cases are sensitive to oestrogen, and ovarian hormone stimulation has been suggested to increase the risk of breast cancer by influencing endogenous oestrogen levels. Previous studies on ART treatment and breast cancer have varied in their findings, but several studies have small sample sizes or lack follow-up time and/or confounder adjustment. Recent childbirth, nulliparity and higher socio-economic status are breast cancer risk factors and the latter two are also associated with initiating ART treatment. STUDY DESIGN, SIZE, DURATION: The Danish National ART-Couple II (DANAC II) cohort includes women treated with ART at public and private fertility clinics in 1994-2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with no cancer prior to ART treatment were included (n = 61 579). Women from the background population with similar age and no prior history of ART treatment were randomly selected as comparisons (n = 579 760). The baseline mean age was 33.1 years (range 18-46 years). Results are presented as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: During follow-up (median 9.69 years among ART-treated and 9.28 years among untreated), 5861 women were diagnosed with breast cancer, 695 among ART-treated and 5166 among untreated women (1.1% versus 0.9%, P < 0.0001). Using Cox regression analyses adjusted for nulliparity, educational level, partnership status, year, maternal breast cancer and age, the risk of breast cancer was slightly increased among women treated with ART (HR 1.14, 95% CI 1.12-1.16). All causes of infertility were slightly associated with breast cancer risk after ART treatment. The risk of breast cancer increased with higher age at ART treatment initiation and was highest among women initiating treatment at age 40+ years (HR 1.37, 95% CI 1.29-1.45). When comparing women with a first birth at age 40+ years with or without ART treatment, the increased risk among women treated with ART persisted (HR 1.51, 95% CI 1.09-2.08). LIMITATIONS, REASONS FOR CAUTION: Although this study is based on a large, national cohort of women, more research with sufficient power and confounder adjustment is needed, particularly in cohorts with a broad age representation. WIDER IMPLICATIONS OF THE FINDINGS: An increased risk of breast cancer associated with a higher age at ART treatment initiation has been shown. Ovarian stimulation may increase the risk of breast cancer among women initiating ART treatment when aged 40+ years. Age-related vulnerability to hormone exposure or higher hormone doses during ART treatment may explain the increased risk. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the DANAC II cohort was received from the Ebba Rosa Hansen Foundation. The authors report no conflict of interest. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Neoplasias da Mama , Infertilidade Feminina , Adolescente , Adulto , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etiologia , Estudos de Coortes , Feminino , Humanos , Infertilidade Feminina/terapia , Pessoa de Meia-Idade , Sistema de Registros , Técnicas de Reprodução Assistida/efeitos adversos , Adulto Jovem
9.
Phys Rev Lett ; 127(27): 273201, 2021 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-35061406

RESUMO

We present experimental data on the nonadiabatic strong field ionization of atomic hydrogen using elliptically polarized femtosecond laser pulses at a central wavelength of 390 nm. Our measured results are in very good agreement with a numerical solution of the time-dependent Schrödinger equation (TDSE). Experiment and TDSE show four above-threshold ionization peaks in the electron's energy spectrum. The most probable emission angle (also known as "attoclock offset angle" or "streaking angle") is found to increase with energy, a trend that is opposite to standard predictions based on Coulomb interaction with the ion. We show that this increase of deflection angle can be explained by a model that includes nonadiabatic corrections of the initial momentum distribution at the tunnel exit and nonadiabatic corrections of the tunnel exit position itself.

10.
Phys Rev Lett ; 126(5): 053202, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33605768

RESUMO

Strong-field ionization of atoms by circularly polarized femtosecond laser pulses produces a donut-shaped electron momentum distribution. Within the dipole approximation this distribution is symmetric with respect to the polarization plane. The magnetic component of the light field is known to shift this distribution forward. Here, we show that this magnetic nondipole effect is not the only nondipole effect in strong-field ionization. We find that an electric nondipole effect arises that is due to the position dependence of the electric field and which can be understood in analogy to the Doppler effect. This electric nondipole effect manifests as an increase of the radius of the donut-shaped photoelectron momentum distribution for forward-directed momenta and as a decrease of this radius for backwards-directed electrons. We present experimental data showing this fingerprint of the electric nondipole effect and compare our findings with a classical model and quantum calculations.

11.
Phys Rev Lett ; 126(8): 083201, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33709766

RESUMO

We investigate the differential ionization probability of chiral molecules in the strong-field regime as a function of the helicity of the incident light. To this end, we analyze the fourfold ionization of bromochlorofluoromethane (CHBrClF) with subsequent fragmentation into four charged fragments and different dissociation channels of the singly ionized methyloxirane. By resolving for the molecular orientation, we show that the photoion circular dichroism signal strength is increased by 2 orders of magnitude.

12.
Phys Rev Lett ; 127(10): 103201, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34533326

RESUMO

We report on a joint experimental and theoretical study of photoelectron circular dichroism (PECD) in methyloxirane. By detecting O 1s photoelectrons in coincidence with fragment ions, we deduce the molecule's orientation and photoelectron emission direction in the laboratory frame. Thereby, we retrieve a fourfold differential PECD clearly beyond 50%. This strong chiral asymmetry is reproduced by ab initio electronic structure calculations. Providing such a pronounced contrast makes PECD of fixed-in-space chiral molecules an even more sensitive tool for chiral recognition in the gas phase.

13.
Infection ; 49(3): 501-509, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33537915

RESUMO

PURPOSE: To predict the course of immune recovery (IR) in HIV-1-infected patients after initiation of combined antiretroviral therapy (cART) by determination of the plasma concentration of Torque Teno Virus (TTV). TTV has been identified as marker for risk assessment in immunosuppressed patients after transplantation procedures. Here, TTV was analyzed in HIV-1-infected therapy-naïve patients to evaluate its use as predictor of the course of IR for guidance of individualized treatment. METHODS: TTV DNA was quantified in plasma samples of 301 therapy-naïve HIV-1-infected patients and correlated to CD4+ cell count, HIV viral load, presence of the herpes viruses CMV, EBV and HHV-8, age and sex. Patients were classified according to their initial CD4+ cell count and to the extent of CD4+ T-cell increase within the first year of cART. RESULTS: TTV DNA was detectable in 96% of the patients' plasma samples with a median TTV plasma concentration of 5.37 log10 cop/ml. The baseline CD4+ cell count was negatively correlated with TTV plasma concentration (p = 0.003). In patients with a CD4+ cell recovery < 50 cells/µl, the median TTV plasma concentration was significantly higher compared to patients with a CD4+ cell recovery of > 200 CD4+ cells/µl (5.68 log10 cop/ml versus 4.99 log10 cop/ml; p = 0.011). TTV plasma concentration in combination with baseline CD4+ cell count were significantly correlated to CD4+ cell recovery (p = 0.004). For all other parameters considered, no significant correlation for CD4+ cell recovery was found. CONCLUSION: Within the cohort, the significantly elevated TTV plasma concentration in patients with diminished CD4+ cell recovery indicates a more profound immune defect. Baseline TTV plasma concentrations and CD4+ cell count are predictive for the course of immune recovery in HIV-1-infected patients with severe immunodeficiency.


Assuntos
Infecções por Vírus de DNA , Infecções por HIV , Torque teno virus , Biomarcadores , DNA Viral , Infecções por HIV/tratamento farmacológico , Humanos , Imunocompetência , Torque teno virus/genética , Carga Viral
14.
Proc Natl Acad Sci U S A ; 115(22): E5243-E5249, 2018 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-29760065

RESUMO

NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate-controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.


Assuntos
Regulação da Expressão Gênica/fisiologia , NF-kappa B/metabolismo , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Linhagem Celular Tumoral , Células Cultivadas , Citocinas/metabolismo , Regulação da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Humanos , Inflamação , Camundongos , NF-kappa B/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Temperatura , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/análise , Proteína 3 Induzida por Fator de Necrose Tumoral alfa/genética
15.
Hum Reprod ; 35(8): 1808-1820, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32696041

RESUMO

STUDY QUESTION: What is the rate of natural conception leading to ongoing pregnancy or livebirth over 6-12 months for infertile women of age ≥35 years? SUMMARY ANSWER: Natural conception rates were still clinically relevant in women aged 35 years and above and were significantly higher in women with unexplained infertility compared to those with other diagnoses. WHAT IS KNOWN ALREADY: In recent years, increasing numbers of women have attempted to conceive at a later age, resulting in a commensurate increase in the need for ART. However, there is a lack of data on natural fertility outcomes (i.e. no interventions) in women with increasing age. STUDY DESIGN, SIZE, DURATION: A systematic review with individual participant data (IPD) meta-analysis was carried out. PubMed, MEDLINE, EMBASE, the Cochrane Library, clinicaltrials.gov were searched until 1 July 2018 including search terms 'fertility service', 'waiting list', 'treatment-independent' and 'spontaneous conception'. Language restrictions were not imposed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were studies (at least partly) reporting on infertile couples with female partner of age ≥35 years who attended fertility services, underwent fertility workup (e.g. history, semen analysis, tubal status and ovulation status) and were exposed to natural conception (e.g. independent of treatment such as IVF, ovulation induction and tubal surgery). Studies that exclusively studied only one infertility diagnosis, without including other women presenting to infertility services for other causes of infertility, were excluded. For studies that met the inclusion criteria, study authors were contacted to provide IPD, after which fertility outcomes for women of age ≥35 years were retrieved. Time to pregnancy or livebirth and the effect of increasing age on fertility outcomes after adjustment for other prognostic factors were analysed. Quality of studies was graded with the Newcastle-Ottawa Scale (non-randomised controlled trials (RCTs)) or the Cochrane Risk of Bias tool (for RCTs). MAIN RESULTS AND THE ROLE OF CHANCE: We included nine studies (seven cohort studies and two RCTs) (n = 4379 women of at least age 35 years), with the observed composite primary outcome of ongoing pregnancy or livebirth occurring in 429 women (9.8%) over a median follow-up of 5 months (25th to 75th percentile: 2.5-8.5 months). Studies were of moderate to high quality. The probability of natural conception significantly decreased with any diagnosis of infertility, when compared with unexplained infertility. We found non-linear effects of female age and duration of infertility on ongoing pregnancy and tabulated the predicted probabilities for unexplained infertile women aged 35-42 years with either primary or secondary infertility and with a duration of infertility from 1 to 6 years. For a 35-year-old woman with 2 years of primary unexplained infertility, the predicted probability of natural conception leading to ongoing pregnancy or livebirth was 0.15 (95% CI 0.11-0.19) after 6 months and 0.24 (95% CI 0.17-0.30) after 12 months. For a 42-year-old woman, this decreased to 0.08 (95% CI 0.04-0.11) after 6 months and 0.13 (95% CI 0.07-0.18) after 12 months. LIMITATIONS, REASONS FOR CAUTION: In the studies selected, there were different study designs, recruitment strategies in different centres, protocols and countries and different methods of assessment of infertility. Data were limited for women above the age of 40 years. WIDER IMPLICATIONS OF THE FINDINGS: Women attending fertility services should be encouraged to pursue natural conception while waiting for treatment to commence and after treatment if it is unsuccessful. Our results may aid in counselling women, and, in particular, for those with unexplained infertility. STUDY FUNDING/COMPETING INTEREST(S): S.J.C. received funding from the University of Adelaide Summer Research Scholarship. B.W.M. is supported by a NHMRC Investigator grant (GNT1176437), B.W.M. reports consultancy for ObsEva, Merck, Merck KGaA, iGenomix and Guerbet. B.W.M. reports research support by Merck and Guerbet. PROSPERO REGISTRATION NUMBER: CRD42018096552.


Assuntos
Fertilidade , Fertilização , Adulto , Pré-Escolar , Feminino , Fertilização in vitro , Humanos , Nascido Vivo , Masculino , Indução da Ovulação , Gravidez , Taxa de Gravidez
16.
Encephale ; 46(3S): S107-S113, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32517998

RESUMO

Emerging infectious diseases like Covid-19 cause a major threat to global health. When confronted with new pathogens, individuals generate several beliefs about the epidemic phenomenon. Many studies have shown that individual protective behaviors largely depend on these beliefs. Due to the absence of treatment and vaccine against these emerging pathogens, the relation between these beliefs and these behaviors represents a crucial issue for public health policies. In the premises of the Covid-19 pandemic, several preliminary studies have highlighted a delay in the perception of risk by individuals, which potentially holds back the implementing of the necessary precautionary measures: people underestimated the risks associated with the virus, and therefore also the importance of complying with sanitary guidelines. During the peak of the pandemic, the salience of the threat and of the risk of mortality could then have transformed the way people generate their beliefs. This potentially leads to upheavals in the way they understand the world. Here, we propose to explore the evolution of beliefs and behaviors during the Covid-19 crisis, using the theory of predictive coding and the theory of terror management, two influential frameworks in cognitive science and in social psychology.


Assuntos
Betacoronavirus , Encéfalo/fisiologia , Infecções por Coronavirus/psicologia , Cultura , Medo/psicologia , Comportamentos Relacionados com a Saúde , Pandemias , Pneumonia Viral/psicologia , Adaptação Psicológica , Atitude Frente a Saúde , COVID-19 , Controle de Doenças Transmissíveis , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/prevenção & controle , Negação em Psicologia , Fidelidade a Diretrizes , Guias como Assunto , Comportamentos de Risco à Saúde , Humanos , Higiene , Modelos Psicológicos , Pandemias/prevenção & controle , Pneumonia Viral/epidemiologia , Pneumonia Viral/prevenção & controle , Equipamentos de Proteção , Gestão de Riscos , Comportamento de Redução do Risco , SARS-CoV-2 , Precauções Universais
17.
Hum Reprod ; 34(11): 2290-2296, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31600391

RESUMO

STUDY QUESTION: Does hormone stimulation during assisted reproductive technology (ART) treatment increase the risk of ovarian cancer? SUMMARY ANSWER: No increased risk of ovarian cancer was found among ART-treated women, with the exception of ART-treated women with endometriosis. WHAT IS KNOWN ALREADY: Previous studies on the association between ovarian stimulation during ART and ovarian cancer have shown conflicting results. The risk of ovarian cancer varies according to the cause of infertility, and only a few studies on ART treatment and risk of ovarian cancer have had sufficient data to address this issue. Endometriosis has been linked to an increased risk of ovarian cancer. STUDY DESIGN, SIZE, DURATION: Women undergoing ART treatment during 1994-2015 were registered in the Danish IVF register. Data were linked with data from the Danish Cancer Register and socio-demographic population registers using an individual person identification number assigned to people residing in Denmark. PARTICIPANTS/MATERIALS, SETTING, METHODS: All women undergoing ART treatment were age-matched with a random sample of the female background population and followed for up to 22 years. After relevant exclusions, the population consisted of 58 472 ART-treated women and 625 330 untreated women, all with no previous malignancies. Ovarian cancer risk was assessed using multivariable cox regression analyses with adjustment for educational level, marital status, parity and treatment year. Results are shown as hazard ratios (HRs) with corresponding CIs. MAIN RESULTS AND THE ROLE OF CHANCE: In total, 393 (0.06%) women were diagnosed with ovarian cancer during follow-up (mean 9.7 years). Women treated with ART had an increased risk of ovarian cancer (HR 1.20, 95% CI 1.10-1.31), which diminished over time. The increased risk was apparent among women with female factor infertility (HR 1.36, 95% CI 1.25-1.48), whereas no female factor infertility was associated with a lower risk (HR 0.87, 95% CI 0.76-1.00). The risk was increased among women with endometriosis (HR 3.78, 95% CI 2.45-5.84), whereas no increased risk was found among ART-treated women with polycystic ovary syndrome, other female causes of infertility and unexplained infertility. LIMITATIONS, REASONS FOR CAUTION: The association between ART treatment and ovarian cancer is likely influenced by increased detection due to multiple ultrasound scans during ART treatment. WIDER IMPLICATIONS OF THE FINDINGS: Undergoing ART treatment without the presence of endometriosis was not associated with an increased risk of ovarian cancer, which is reassuring. Whether ART treatment increases the risk of ovarian cancer among women with endometriosis needs further investigation. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a PhD grant to D.V. from the Faculty of Health and Medical Sciences, University of Copenhagen, Denmark. Funding for establishing the Danish National ART-couple II cohort was achieved from Ebba Rosa Hansen Foundation. The funders had no influence on data collection, analyses or results presented. The authors have no conflicts of interest to declare.


Assuntos
Endometriose/complicações , Infertilidade Feminina/complicações , Neoplasias Ovarianas/etiologia , Técnicas de Reprodução Assistida/efeitos adversos , Adulto , Dinamarca/epidemiologia , Endometriose/terapia , Feminino , Fertilização in vitro , Seguimentos , Humanos , Infertilidade Feminina/terapia , Modelos de Riscos Proporcionais , Sistema de Registros , Análise de Regressão , Risco , Medição de Risco
18.
Hum Reprod ; 34(4): 679-688, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30811549

RESUMO

STUDY QUESTION: What are the attitudes towards different aspects of a freeze-all strategy and elective frozen embryo transfer (eFET) in comparison with fresh embryo transfer in assisted reproductive technology treatment among female and male patients before and after their first ART treatment cycle in a public health care setting? SUMMARY ANSWER: Despite concerns about the delay in embryo transfer associated with eFET, nearly 60% of the participants were in favor of eFET compared with fresh embryo transfer assuming that the clinical pregnancy rate was equivalent. WHAT IS KNOWN ALREADY: Vitrification and blastocyst transfer have considerably improved success rates after FET with ongoing pregnancy rates in frozen cycles approaching those seen in fresh treatment cycles. Furthermore, the risk of ovarian hyperstimulation syndrome (OHSS) is essentially eliminated in FET cycles, and FET may be beneficial to the endometrial and fetal development because a hormonal environment mirroring the natural cycle is enabled. However, the freeze-all strategy is not yet implemented as standard care. One reason is the presumption of negative patient attitudes towards a freeze-all embryo strategy. So far, no data regarding patients' attitudes on a freeze-all strategy have been published. STUDY DESIGN, SIZE, DURATION: This study was designed as a descriptive cross-sectional study including 165 fertility patients referred for their first ART treatment from December 2014 to June 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: All newly referred patients participating in a mandatory meeting before initiating ART treatment at the Fertility Clinic, Hvidovre Hospital, Copenhagen, Denmark were requested to fill in an online web-based questionnaire separately for men and women covering attitudes towards a freeze-all strategy, socio-demographic data and reproductive history. The patients were informed about both conventional fresh embryo transfer strategy and the freeze-all strategy prior to answering the questionnaire. MAIN RESULTS AND THE ROLE OF CHANCE: The total response rate was 77.1% (n = 165), and for women and men respectively 85.8 versus 66.0%. The female respondents were significantly more likely to consider the postponement of embryo transfer difficult compared to the male population (78.6 versus 35.5%; P < 0.001) and they were significantly more willing to accept a risk in treatment on own health to achieve a pregnancy than were the male respondents on their partners health (82.5 versus 96.8%; P = 0.025). However, 59.2% of the women and 59.7% of the men agreed that they would choose eFET over fresh embryo transfer if the chance of pregnancy were the same. Most of the patients furthermore agreed that the health of the mother and their baby was of highest importance. In the adjusted analyses we found no significant predictive factors for preferences towards a freeze-all strategy apart from a negative attitude towards delay of transfer in case of previous unsuccessful ART attempts. LIMITATIONS, REASONS FOR CAUTION: Selection bias cannot be excluded, as the total response rate was 77.1%. The hypothetical nature of the items may furthermore limit the validity of the results. In addition, the participants were from a single Fertility Clinic in the Capital Region of Denmark and may therefore not be representative for all fertility patients. WIDER IMPLICATIONS OF THE FINDINGS: In a clinical setting with similar pregnancy rates for eFET and fresh embryo transfer, these results indicate that patients, when given access to information on advantages and disadvantages of both fresh embryo transfer and eFET, are less prone to opt for fresh embryo transfer. This may be ground breaking for a patient-centered paradigm shift in routine ART treatment with a wider implementation of a freeze-all and eFET-strategy eliminating the risk of OHSS. STUDY FUNDING/COMPETING INTEREST(S): The Danish Council for Independent Research and Merck Serono supported the study. The study is part of the Reprounion Collaborative study, co-financed by the European Union, Interreg V ÖKS. No competing interests exist.


Assuntos
Atitude , Blastocisto , Criopreservação/métodos , Transferência Embrionária/métodos , Fertilização in vitro/métodos , Preferência do Paciente/psicologia , Técnicas de Reprodução Assistida/psicologia , Adulto , Estudos Transversais , Dinamarca , Feminino , Seguimentos , Humanos , Masculino , Síndrome de Hiperestimulação Ovariana , Gravidez , Taxa de Gravidez , Inquéritos e Questionários , Vitrificação
19.
Hum Reprod ; 34(2): 291-296, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30561641

RESUMO

STUDY QUESTION: What do couples referred to or attending a recurrent pregnancy loss (RPL) clinic believe they need in terms of treatment, support and follow up? SUMMARY ANSWER: Men and women wish for more information, earlier access to treatment, support and follow up that is sensitive to their history of pregnancy loss (PL), includes both members of the couple, and acknowledges the psychological impact of RPL. WHAT IS KNOWN ALREADY: Previous research has highlighted women's dissatisfaction with medical care provided post-PL and their desire for medical professionals to have increased awareness about PL and recognition of the psychological impact of PL. Less is known about the needs of the male partner, the needs of those experiencing RPL and whether the needs differ during different reproductive stages. STUDY DESIGN, SIZE, DURATION: Over a 2-month period in 2017-2018, 13 couples who were referred to the national RPL program in Copenhagen, Denmark were qualitatively interviewed. PARTICIPANTS/MATERIALS, SETTING, METHODS: Inclusion criteria were heterosexual couples with at least three consecutive PLs before 12 weeks' gestation with no children or one child prior to the PLs, not currently pregnant, and willing to be interviewed in English. Couples were interviewed together in a semi-structured format. Data were analyzed using thematic analysis. Invitations (n = 30) were sent to couples recently referred to the RPL program who indicated an interest in participating and 17 couples contacted the interviewer to schedule an interview. Due to cancellations, 15 interviews were held. Data from 13 interviews that met the study criteria were used for the current analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The participants had experienced a median of three PLs (range 3-6). Both men and women described the cumulative effect of RPL with an increase in pressure and exhaustion by the third and subsequent losses. Inclusion of the male partner in consultations and treatment was seen as important. Men felt pressured to remain positive and support their partners despite their own feelings of loss. The findings showed that couples desired reliable and accurate information about RPL. They wished for recognition from the medical community that RPL has a significant psychological impact, and stressed that effective treatment should include both members of the couple, with attention to both physical and psychological aspects of the RPL and should be tailored to their current reproductive stage, in order to help them cope with the negative impact of RPL and the anxiety associated with conception and another pregnancy. LIMITATIONS, REASONS FOR CAUTION: Participants were self-selected thus findings cannot be generalized to all couples with RPL. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study addressing the needs of the female and male partners in couples suffering from RPL. The findings highlight a disconnect between couples' perceived needs and their experience of medical care after RPL. This may be partly due to a discrepancy in couples' and medical professionals' perceptions of the PLs. The findings highlight that medical professionals need to take a holistic and couple-focused approach in their treatment of RPL and include attention to the psychological impact and cumulative effect of the multiple PLs on the couple. The results underscore the need for informational resources and psychological support for couples experiencing RPL, tailored to their reproductive stage. STUDY FUNDING/COMPETING INTEREST(S): EK was funded by a Travel/Training Fellowship from ReproUnion, co-financed by the European Union, Interreg V ÖKS. No other competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Aborto Habitual/reabilitação , Adaptação Psicológica , Assistência ao Convalescente/psicologia , Ansiedade/terapia , Estresse Psicológico , Aborto Habitual/psicologia , Acesso à Informação/psicologia , Adulto , Ansiedade/etiologia , Ansiedade/psicologia , Estudos Transversais , Dinamarca , Feminino , Conhecimentos, Atitudes e Prática em Saúde , Humanos , Masculino , Gravidez , Sistemas de Apoio Psicossocial , Pesquisa Qualitativa , Resultado do Tratamento
20.
Phys Rev Lett ; 123(19): 193001, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31765203

RESUMO

We investigate K-shell ionization of N_{2} at 40 keV photon energy. Using a cold target recoil ion momentum spectroscopy reaction microscope, we determine the vector momenta of the photoelectron, the Auger electron, and both N^{+} fragments. These fully differential data show that the dissociation process of the N_{2}^{2+} ion is significantly modified not only by the recoil momentum of the photoelectron but also by the photon momentum and the momentum of the emitted Auger electron. We find that the recoil energy introduced by the photon and the photoelectron momentum is partitioned with a ratio of approximately 30∶70 between the Auger electron and fragment ion kinetic energies, respectively. We also observe that the photon momentum induces an additional rotation of the molecular ion.

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