Mortality of midlife women with surgically verified endometriosis-a cohort study including 2.5 million person-years of observation

STUDY QUESTION Is all-cause and cause-specific mortality increased among women with surgically verified endometriosis? SUMMARY ANSWER The all-cause and cause-specific mortality in midlife was lower throughout the follow-up among women with surgically verified endometriosis compared to the reference cohort. WHAT IS KNOWN ALREADY Endometriosis has been associated with an increased risk of comorbidities such as certain cancers and cardiovascular diseases. These diseases are also common causes of death; however, little is known about the mortality of women with endometriosis. STUDY DESIGN, SIZE, DURATION A nationwide retrospective cohort study of women with surgically verified diagnosis of endometriosis was compared to the reference cohort in Finland (1987-2012). Follow-up ended at death or 31 December 2014. During the median follow-up of 17years, 2.5 million person-years accumulated. PARTICIPANTS/MATERIALS, SETTING, METHODS Forty-nine thousand nine hundred and fifty-six women with at least one record of surgically verified diagnosis of endometriosis in the Finnish Hospital Discharge Register between 1987 and 2012 were compared to a reference cohort of 98824 age- and municipality-matched women. The age (meanstandard deviation) of the endometriosis cohort was 36.49.0 and 53.612.1years at the beginning and at the end of the follow-up, respectively. By using the Poisson regression models the crude and adjusted all-cause and cause-specific mortality rate ratios (MRR) and 95% confidence intervals (CI) were assessed. Calendar time, age, time since the start of follow-up, educational level, and parity adjusted were considered in the multivariate analyses. MAIN RESULTS AND THE ROLE OF CHANCE A total of 1656 and 4291 deaths occurred in the endometriosis and reference cohorts, respectively. A lower all-cause mortality was observed for the endometriosis cohort (adjusted MRR, 0.73 [95% CI 0.69 to 0.77])-there were four deaths less per 1000 women over 10years. A lower cause-specific mortality contributed to this: the adjusted MRR was 0.88 (95% CI 0.81 to 0.96) for any cancer and 0.55 (95% CI 0.47 to 0.65) for cardiovascular diseases, including 0.52 (95% CI 0.42 to 0.64) for ischemic heart disease and 0.60 (95% CI 0.47 to 0.76) for cerebrovascular disease. Mortality due to alcohol, accidents and violence, respiratory, and digestive disease-related causes was also decreased. LIMITATIONS, REASONS FOR CAUSATION These results are limited to women with endometriosis diagnosed by surgery. In addition, the study does not extend into the oldest age groups. The results might be explained by the characteristics and factors related to women's lifestyle, and/or increased medical attention and care received, rather than the disease itself. WIDER IMPLICATIONS OF THE FINDINGS These reassuring data are valuable to women with endometriosis and to their health care providers. Nonetheless, more studies are needed to address the causality. STUDY FUNDING/COMPETING INTEREST This research was funded by the Hospital District of Helsinki and Uusimaa and The Finnish Medical Foundation. None of the authors report any competing interest in relation to the present work; all the authors have completed the disclosure form.Peer reviewe

Mortality in individuals with intellectual disabilities in Finland

Objectives: This study aimed at ascertaining the standardized mortality ratios (SMR) for those with an intellectual disability (ID) in Finland. Materials and Methods: We used the statistical database of the national insurance institution of Finland and Statistics Finland&#39;s mean population figures. We determined the number of individuals who received benefits (disability allowance, disability pension, or care allowance for pensioners) due to an ID diagnosis and the number of those whose benefit had been terminated due to death during the years 1996-2011. Results: SMR for females with a mild ID (IQ 50-69) was 2.8 (95% CI: 2.60-3.01) and for males 2.0 (95% CI: 1.88-2.14), and for females with a severe ID (IQ &lt; 50) 5.2 (95% CI: 4.99-5.50) and for males 2.6 (95% CI: 2.48-2.72). Conclusion: This significant difference in the SMR figures between males and females with ID warrants further research.</p

Adolescent attachment to parents and peers in singletons and twins born with assisted and natural conception

STUDY QUESTION Does adolescent attachment to parents and peers differ between singletons and twins born with ART or natural conception (NC)? SUMMARY ANSWER Adolescent attachment anxiety with the father was higher among NC singletons than among ART and NC twins, whereas attachment avoidance with the father was higher in ART singletons than in NC singletons and NC twins. No differences were found in attachment to the mother, best friend or romantic partner. WHAT IS KNOWN ALREADY Most studies have not found differences between ART and NC singletons in parent-adolescent relationships, but twin relationships may be more at risk. No previous study has examined all four groups in the same study, or specifically looked at attachment relationships. STUDY DESIGN, SIZE, DURATION This was an 18-year, prospective and controlled longitudinal study with families of 496 ART singletons, 101 ART twin pairs, 476 NC singletons and 22 NC twin pairs. Families were recruited during the second trimester of pregnancy; the ART group was recruited from five infertility clinics in Finland and the control group was recruited from a hospital outpatient clinic during a routine visit. PARTICIPANTS/MATERIALS, SETTING, METHODS Mothers and fathers gave background information for this study during pregnancy, and during the child's first year and early school age (7-8 years). For the ART group, infertility characteristics and prenatal medical information was also obtained from the patient registry of the infertility clinics. Children (originally 50% girls) filled in electronic questionnaires related to their attachment to mother, father, best friend and romantic partner (Experiences in Close Relationships-Relationship Structures) at 17-19 years of age. MAIN RESULTS AND THE ROLE OF CHANCE Adolescent attachment anxiety to father was higher in NC singletons than in ART twins, P = 0.004 and marginally higher than in NC twins, P = 0.06. Adolescent attachment avoidance to father was higher in ART singletons than in NC singletons, P = 0.006 and marginally higher than in NC twins, P = 0.055. LIMITATIONS, REASONS FOR CAUTION The sample size was small especially in the NC twin group and there was drop-out over the 18-year time period, especially among boys and families with lower parental education level. The study only included native Finnish-speaking families. The results could differ in a more diverse population. ART singletons were younger and had fewer siblings than ART twins and NC children, and ART and NC twins had more newborn health risks than ART and NC singletons. WIDER IMPLICATIONS OF THE FINDINGS The study adds to a growing body of evidence that neither ART treatments nor being a twin places mother-child relationships or peer relationships at long-term risk. However, in our study, which was the first to examine both ART and twinhood simultaneously, we found that there may be more problems in father-adolescent relationships, but only in ART singletons and only related to attachment avoidance. Our findings suggest that men, as well as women, should receive enough support in pre- and peri-natal health care during and after infertility treatments. STUDY FUNDING/COMPETING INTEREST(S) This study was funded by Academy of Finland (grant number 2501308988), the Juho Vainio Foundation and the Finnish Cultural Foundation. The authors report no conflict of interest.Peer reviewe

Puberty disorders among ART-conceived singletons : a Nordic register study from the CoNARTaS group

STUDY QUESTION Do ART-conceived children have an increased risk for puberty disorders? SUMMARY ANSWER Both ART-conceived boys and girls had a higher risk of puberty disorders; early puberty was more common among girls and late puberty among boys. WHAT IS KNOWN ALREADY Some physiological differences in growth and metabolism have been reported for ART-conceived children compared to non-ART-conceived children. Knowledge on pubertal development and disorders in ART-conceived children is limited. STUDY DESIGN, SIZE, DURATION A register-based cohort study was carried out including data from 1985 to 2015. The Committee of Nordic Assisted Reproductive Technology and Safety (CoNARTaS) study population consists of all live and stillborn children, as well as their mothers, registered in the Medical Birth Registers during the study period in Denmark, Sweden, Finland and Norway. PARTICIPANTS/MATERIALS, SETTING, METHODS A total of 122 321 ART-conceived singletons and 6 576 410 non-ART singletons born in Denmark (1994-2014), Finland (1990-2014), Norway (2002-2015) and Sweden (1985-2015) were included. Puberty disorders were defined using International Classification of Diseases and Related Health Problems (ICD)-9/ICD-10 codes and classified in the following groups: late puberty (6268/E30.0), early puberty (2591 and 2958/E30.1 and E30.8) and unspecified disorders (V212 and V579/E30.9 and Z00.3 as well as Z51.80 for Finland). The results in Cox regression were adjusted for maternal age, parity, smoking, gestational diabetes, chronic hypertension, hypertensive disorders during pregnancy and country, and further for either gestational age, birthweight, small for gestational age or large for gestational age. MAIN RESULTS AND THE ROLE OF CHANCE There were 37 869 children with diagnoses related to puberty disorders, and 603 of them were born after ART. ART-conceived children had higher risks for early (adjusted hazard ratio (aHR) 1.45, 95% CI: 1.29-1.64) and late puberty (aHR 1.47, 95% CI: 1.21-1.77). Girls had more diagnoses related to early puberty (aHR 1.46, 95% CI: 1.29-1.66) and boys with late puberty (aHR 1.55, 95% CI: 1.24-1.95). LIMITATIONS, REASONS FOR CAUTION Using reported puberty disorders with ICD codes in health care registers might vary, which may affect the numbers of cases found in the registers. Register data may give an underestimation both among ART and non-ART-conceived children, especially among non-ART children, who may not be as carefully followed as ART-conceived children. Adjustment for causes and duration of infertility, mothers' own puberty characteristics and BMI, as well as children's BMI, was not possible because data were not available or data were missing for the early years. It was also not possible to compare ART to non-ART siblings or to study the pubertal disorders by cause of subfertility owing to a small number of discordant sibling pairs and a large proportion of missing data on cause of subfertility. WIDER IMPLICATIONS OF THE FINDINGS This large, register-based study suggests that ART-conceived children have a higher risk for puberty disorders. However, the mechanisms of infertility and pubertal onset are complex, and ART is a rapidly advancing field with various treatment options. Studying the pubertal disorders of ART-conceived offspring is a continuing challenge. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by the Nordic Trial Alliance: a pilot project jointly funded by the Nordic Council of Ministers and NordForsk (71450), the Central Norway Regional Health Authorities (46045000), the Nordic Federation of Obstetrics and Gynaecology (NF13041, NF15058, NF16026 and NF17043), the Interreg oresund-Kattegat-Skagerrak European Regional Development Fund (ReproUnion project), the Research Council of Norway's Centre of Excellence funding scheme (262700), the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-70940) and FLUX Consortium 'Family Formation in Flux-Causes, Consequences and Possible Futures', funded by the Strategic Research Council, Academy of Finland (DEMOGRAPHY 345130). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. The authors have no conflicts of interest to disclose.Peer reviewe

Time trends in placenta-mediated pregnancy complications after assisted reproductive technology in the Nordic countries

Background The use of assisted reproductive technology (ART) is increasing worldwide and conception after assisted reproduction currently comprises 3-6% of birth cohorts in the Nordic countries. The risk of placenta-mediated pregnancy complications is higher after ART compared to spontaneously conceived pregnancies. Whether the excess risk of placenta-mediated pregnancy complications in pregnancies following assisted reproduction has changed over time, is unknown. Objectives To investigate whether time trends in risk of pregnancy complications (hypertensive disorders in pregnancy, placental abruption and placenta previa) differ for pregnancies after ART compared to spontaneously conceived pregnancies during three decades of assisted reproduction treatment in the Nordic countries. Study Design In a population-based cohort study, with data from national health registries in Denmark (1994-2014), Finland (1990-2014), Norway (1988-2015) and Sweden (1988-2015), we included 6,830,578 pregnancies resulting in delivery. Among these, 146,998 (2.2%) were pregnancies after assisted reproduction (125,708 singleton pregnancies, 20,668 twin pregnancies and 622 of higher order plurality) and 6,683,132 (97.8%) pregnancies were conceived spontaneously (6,595,185 singleton pregnancies, 87,106 twin pregnancies and 1,289 of higher order plurality). We used logistic regression with post-estimation to estimate absolute risks and risk differences for each complication. We repeated analyses for singleton and twin pregnancies, separately. In sub-samples with available information, we also adjusted for maternal body mass index, smoking during pregnancy, previous cesarean section, culture duration and cryopreservation. Results The risk of each placental complication was consistently higher in pregnancies following ART compared to spontaneously conceived pregnancies across the study period, except for hypertensive disorders in twin pregnancies, where risks were similar. Risk of hypertensive disorders increased over time in twin pregnancies for both conception methods, but more strongly for pregnancies following ART (risk difference 1.73 percentage points per 5 years, 95% confidence interval 1.35 to 2.11) than for spontaneously conceived twins (risk difference 0.75 percentage points, 95% confidence interval 0.61 to 0.89). No clear time trends were found for hypertensive disorders in singleton pregnancies. Risk of placental abruption decreased over time in all groups (risk difference -0.16 percentage points, 95% confidence interval -0.19 to -0.12 and -0.06 percentage points, 95% confidence interval -0.06 to -0.05 for pregnancies after assisted reproduction and spontaneously conceived pregnancies, respectively, for singletons and multiple pregnancies combined). Over time, the risk of placenta previa increased in pregnancies after assisted reproduction among both singletons (risk difference 0.21 percentage points, 95% confidence interval 0.14 to 0.27) and twins (risk difference 0.30 percentage points, 95% confidence interval 0.16 to 0.43), but remained stable in spontaneously conceived pregnancies. When adjusting for culture duration, the temporal increase in placenta previa became weaker in all groups of ART pregnancies, whereas adjustment for cryopreservation moderately attenuated trends in ART twin pregnancies. Conclusions The risk of placenta-mediated pregnancy complications following ART remains higher compared to spontaneously conceived pregnancies, despite declining rates of multiple pregnancies. For hypertensive disorders in pregnancy and placental abruption, pregnancies after assisted reproduction follow the same time trends as the background population, whereas for placenta previa, risk has increased over time in pregnancies after ART.Peer reviewe

Trends over time in congenital malformations in live-born children conceived after assisted reproductive technology

IntroductionChildren born after assisted reproductive technology, particularly singletons, have been shown to have an increased risk of congenital malformations compared with children born after spontaneous conception. We wished to study whether there has been a change in the past 20 years in the risk of major congenital malformations in children conceived after assisted reproductive technology compared with children spontaneously conceived. Material and methodsPopulation-based cohort study including 90 201 assisted reproductive technology children and 482 552 children spontaneously conceived, born in Denmark, Finland, Norway and Sweden. Both singletons and twins born after in vitro fertilization, intracytoplasmatic sperm injection and frozen embryo transfer were included. Data on children were taken from when the national Nordic assisted reproductive technology registries were established until 2007. Multiple logistic regression analyses were used to estimate the risks and adjusted odds ratios for congenital malformations in four time periods: 1988-1992, 1993-1997, 1998-2002 and 2003-2007. Only major malformations were included. ResultsThe absolute risk for singletons of being born with a major malformation was 3.4% among assisted reproductive technology children vs. 2.9% among children spontaneously conceived during the study period. The relative risk of being born with a major congenital malformation between all assisted reproductive technology children and children spontaneously conceived remained similar through all four time periods (p = 0.39). However, we found that over time the number of children diagnosed with a major malformation increased in both groups across all four time periods. ConclusionWhen comparing children conceived after assisted reproductive technology and spontaneously conceived, the relative risk of being born with a major congenital malformation did not change during the study period.Peer reviewe

Sensitivity of the human auditory cortex to acoustic degradation of speech and non-speech sounds

The perception of speech is usually an effortless and reliable process even in highly adverse listening conditions. In addition to external sound sources, the intelligibility of speech can be reduced by degradation of the structure of speech signal itself, for example by digital compression of sound. This kind of distortion may be even more detrimental to speech intelligibility than external distortion, given that the auditory system will not be able to utilize sound source-specific acoustic features, such as spatial location, to separate the distortion from the speech signal. The perceptual consequences of acoustic distortions on speech intelligibility have been extensively studied. However, the cortical mechanisms of speech perception in adverse listening conditions are not well known at present, particularly in situations where the speech signal itself is distorted. The aim of this thesis was to investigate the cortical mechanisms underlying speech perception in conditions where speech is less intelligible due to external distortion or as a result of digital compression. In the studies of this thesis, the intelligibility of speech was varied either by digital compression or addition of stochastic noise. Cortical activity related to the speech stimuli was measured using magnetoencephalography (MEG). The results indicated that degradation of speech sounds by digital compression enhanced the evoked responses originating from the auditory cortex, whereas addition of stochastic noise did not modulate the cortical responses. Furthermore, it was shown that if the distortion was presented continuously in the background, the transient activity of auditory cortex was delayed. On the perceptual level, digital compression reduced the comprehensibility of speech more than additive stochastic noise. In addition, it was also demonstrated that prior knowledge of speech content enhanced the intelligibility of distorted speech substantially, and this perceptual change was associated with an increase in cortical activity within several regions adjacent to auditory cortex. In conclusion, the results of this thesis show that the auditory cortex is very sensitive to the acoustic features of the distortion, while at later processing stages, several cortical areas reflect the intelligibility of speech. These findings suggest that the auditory system rapidly adapts to the variability of the auditory environment, and can efficiently utilize previous knowledge of speech content in deciphering acoustically degraded speech signals.Puheen havaitseminen on useimmiten vaivatonta ja luotettavaa myös erittäin huonoissa kuunteluolosuhteissa. Puheen ymmärrettävyys voi kuitenkin heikentyä ympäristön häiriölähteiden lisäksi myös silloin, kun puhesignaalin rakennetta muutetaan esimerkiksi pakkaamalla digitaalista ääntä. Tällainen häiriö voi heikentää ymmärrettävyyttä jopa ulkoisia häiriöitä voimakkaammin, koska kuulojärjestelmä ei pysty hyödyntämään äänilähteen ominaisuuksia, kuten äänen tulosuuntaa, häiriön erottelemisessa puheesta. Akustisten häiriöiden vaikutuksia puheen havaitsemiseen on tutkttu laajalti, mutta havaitsemiseen liittyvät aivomekanismit tunnetaan edelleen melko puutteelisesti etenkin tilanteissa, joissa itse puhesignaali on laadultaan heikentynyt. Tämän väitöskirjan tavoitteena oli tutkia puheen havaitsemisen aivomekanismeja tilanteissa, joissa puhesignaali on vaikeammin ymmärrettävissä joko ulkoisen äänilähteen tai digitaalisen pakkauksen vuoksi. Väitöskirjan neljässä osatutkimuksessa lyhyiden puheäänien ja jatkuvan puheen ymmärrettävyyttä muokattiin joko digitaalisen pakkauksen kautta tai lisäämällä puhesignaaliin satunnaiskohinaa. Puheärsykkeisiin liittyvää aivotoimintaa tutkittiin magnetoenkefalografia-mittauksilla. Tutkimuksissa havaittiin, että kuuloaivokuorella syntyneet herätevasteet voimistuivat, kun puheääntä pakattiin digitaalisesti. Sen sijaan puheääniin lisätty satunnaiskohina ei vaikuttanut herätevasteisiin. Edelleen, mikäli puheäänien taustalla esitettiin jatkuvaa häiriötä, kuuloaivokuoren aktivoituminen viivästyi häiriön intensiteetin kasvaessa. Kuuntelukokeissa havaittiin, että digitaalinen pakkaus heikentää puheäänien ymmärrettävyyttä voimakkaammin kuin satunnaiskohina. Lisäksi osoitettiin, että aiempi tieto puheen sisällöstä paransi merkittävästi häiriöisen puheen ymmärrettävyyttä, mikä heijastui aivotoimintaan kuuloaivokuoren viereisillä aivoalueilla siten, että ymmärrettävä puhe aiheutti suuremman aktivaation kuin heikosti ymmärrettävä puhe. Väitöskirjan tulokset osoittavat, että kuuloaivokuori on erittäin herkkä puheäänien akustisille häiriöille, ja myöhemmissä prosessoinnin vaiheissa useat kuuloaivokuoren viereiset aivoalueet heijastavat puheen ymmärrettävyyttä. Tulosten mukaan voi olettaa, että kuulojärjestelmä mukautuu nopeasti ääniympäristön vaihteluihin muun muassa hyödyntämällä aiempaa tietoa puheen sisällöstä tulkitessaan häiriöistä puhesignaalia

Body size modifies the relationship between maternal serum 25-hydroxyvitamin D concentrations and gestational diabetes in high-risk women

Obesity increases the risk of low 25-hydroxyvitamin D (25(OH) D) concentrations and gestational diabetes (GDM). We explored whether the association between GDM and change in 25(OH) D concentrations measured in the first (7-18 wk) and second (20-27 wk) trimesters of pregnancy is dependent on maternal BMI. The study was a prospective study of 219 women with BMI of >= 30 kg/m2, a history of GDM, or both. The participants were stratified by first-trimester BMI: BMI of = 35 kg/m(2). In the BMI group >= 35 kg/m(2), those who did not develop GDM during the follow-up showed higher increase in serum 25(OH) D concentrations compared with women who developed GDM (43.2 vs. 11.5%; P <0.001). No associations between 25(OH) D concentrations and GDM were observed in other BMI groups. These findings give an important aspect of the role of maternal body size in the association between vitamin D and GDM in high-risk women.Peer reviewe

The neurochemical basis of human cortical auditory processing: combining proton magnetic resonance spectroscopy and magnetoencephalography

BACKGROUND: A combination of magnetoencephalography and proton magnetic resonance spectroscopy was used to correlate the electrophysiology of rapid auditory processing and the neurochemistry of the auditory cortex in 15 healthy adults. To assess rapid auditory processing in the left auditory cortex, the amplitude and decrement of the N1m peak, the major component of the late auditory evoked response, were measured during rapidly successive presentation of acoustic stimuli. We tested the hypothesis that: (i) the amplitude of the N1m response and (ii) its decrement during rapid stimulation are associated with the cortical neurochemistry as determined by proton magnetic resonance spectroscopy. RESULTS: Our results demonstrated a significant association between the concentrations of N-acetylaspartate, a marker of neuronal integrity, and the amplitudes of individual N1m responses. In addition, the concentrations of choline-containing compounds, representing the functional integrity of membranes, were significantly associated with N1m amplitudes. No significant association was found between the concentrations of the glutamate/glutamine pool and the amplitudes of the first N1m. No significant associations were seen between the decrement of the N1m (the relative amplitude of the second N1m peak) and the concentrations of N-acetylaspartate, choline-containing compounds, or the glutamate/glutamine pool. However, there was a trend for higher glutamate/glutamine concentrations in individuals with higher relative N1m amplitude. CONCLUSION: These results suggest that neuronal and membrane functions are important for rapid auditory processing. This investigation provides a first link between the electrophysiology, as recorded by magnetoencephalography, and the neurochemistry, as assessed by proton magnetic resonance spectroscopy, of the auditory cortex

Fatty Acid Composition of Developing Sea Buckthorn (Hippophae rhamnoides L.) Berry and the Transcriptome of the Mature Seed

Background: Sea buckthorn (Hippophae rhamnoides L.) is a hardy, fruit-producing plant known historically for its medicinal and nutraceutical properties. The most recognized product of sea buckthorn is its fruit oil, composed of seed oil that is rich in essential fatty acids, linoleic (18:2\u3c9-6) and \u3b1-linolenic (18:3\u3c9-3) acids, and pulp oil that contains high levels of monounsaturated palmitoleic acid (16:1\u3c9-7). Sea buckthorn is fast gaining popularity as a source of functional food and nutraceuticals, but currently has few genomic resources; therefore, we explored the fatty acid composition of Canadian-grown cultivars (ssp. mongolica) and the sea buckthorn seed transcriptome using the 454 GS FLX sequencing technology. Results: GC-MS profiling of fatty acids in seeds and pulp of berries indicated that the seed oil contained linoleic and \u3b1-linolenic acids at 33-36% and 30-36%, respectively, while the pulp oil contained palmitoleic acid at 32-42%. 454 sequencing of sea buckthorn cDNA collections from mature seeds yielded 500,392 sequence reads, which identified 89,141 putative unigenes represented by 37,482 contigs and 51,659 singletons. Functional annotation by Gene Ontology and computational prediction of metabolic pathways indicated that primary metabolism (protein>nucleic acid>carbohydrate>lipid) and fatty acid and lipid biosynthesis pathways were highly represented categories. Sea buckthorn sequences related to fatty acid biosynthesis genes in Arabidopsis were identified, and a subset of these was examined for transcript expression at four developing stages of the berry. Conclusion: This study provides the first comprehensive genomic resources represented by expressed sequences for sea buckthorn, and demonstrates that the seed oil of Canadian-grown sea buckthorn cultivars contains high levels of linoleic acid and \u3b1-linolenic acid in a close to 1:1 ratio, which is beneficial for human health. These data provide the foundation for further studies on sea buckthorn oil, the enzymes involved in its biosynthesis, and the genes involved in the general hardiness of sea buckthorn against environmental conditions.Peer reviewed: YesNRC publication: Ye