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

The interpretation of low mood and worry by high users of secondary care with medically unexplained symptoms

DA - 20111021 IS - 1471-2296 (Electronic) IS - 1471-2296 (Linking) LA - eng PT - Journal Article SB - IMPeer reviewedPublisher PD

The derivation of the formyl-group oxygen of chlorophyll b in higher plants from molecular oxygen.

The mechanism of formation of the formyl group of chlorophyll b has long been obscure but, in this paper, the origin of the 7-formyl-group oxygen of chlorophyll b in higher plants was determined by greening etiolated maize leaves, excised from dark-grown plants, by illumination under white light in the presence of either H218O or 18O2 and examining the newly synthesized chlorophylls by mass spectroscopy. To minimize the possible loss of 18O label from the 7-formyl substituent by reversible formation of chlorophyll b-71-gem-diol (hydrate) with unlabelled water in the cell, the formyl group was reduced to a hydroxymethyl group during extraction with methanol containing NaBH4: chlorophyll a remained unchanged during this rapid reductive extraction process. Mass spectra of chlorophyll a and [7-hydroxymethyl]-chlorophyll b extracted from leaves greened in the presence of either H218O or 18O2 revealed that 18O was incorporated only from molecular oxygen but into both chlorophylls: the mass spectra were consistent with molecular oxygen providing an oxygen atom not only for incorporation into the 7-formyl group of chlorophyll b but also for the well-documented incorporation into the 131-oxo group of both chlorophylls a and b [see Walker, C. J., Mansfield, K. E., Smith, K. M. & Castelfranco, P. A. (1989) Biochem. J. 257, 599–602]. The incorporation of isotope led to as much as 77% enrichment of the 131-oxo group of chlorophyll a: assuming identical incorporation into the 131 oxygen of chlorophyll b, then enrichment of the 7-formyl oxygen was as much as 93%. Isotope dilution by re-incorporation of photosynthetically produced oxygen from unlabelled water was negligible as shown by a greening experiment in the presence of 3-(3,4-dichlorophenyl)-1,1-dimethylurea. The high enrichment using 18O2, and the absence of labelling by H218O, unequivocally demonstrates that molecular oxygen is the sole precursor of the 7-formyl oxygen of chlorophyll b in higher plants and strongly suggests a single pathway for the formation of the chlorophyll b formyl group involving the participation of an oxygenase-type enzyme

Depression and Anxiety Correlate Differently with Salivary Free Cortisol in the Morning in Patients with Functional Somatic Syndrome

Patients presenting with functional somatic syndrome (FSS) are common, and the symptoms are persistent and difficult to treat for doctors and costly for society. The aim of this study was to clarify the common pathophysiology of FSS, especially the relationship between hypothalamic-pituitary-adrenal (HPA) axis function and psychological characteristics of patients with FSS. The subjects were 45 patients with FSS and 29 healthy controls. Salivary free cortisol was measured in the morning, and psychological tests examining depression, anxiety and quality of life (QOL) were performed on the same day. In patients with FSS, depressive scores showed a significant negative correlation with salivary free cortisol in the morning, although in healthy controls, cortisol showed a significant positive correlation with depressive scores. In addition, the correlation between other psychological test scores and cortisol secretion in patients with FSS contrasted with that of controls. The relationship between cortisol and depression, anxiety or QOL, suggests that the HPA axis of patients with FSS is dysfunctional and does not function properly when patients with FSS are under stress. This dysfunction may explain the pathology of medically unexplained persistent symptoms of patients with FSS

Psychological and physical correlates of musculoskeletal symptoms in male professional divers and offshore workers

Background: Underwater divers are more likely to complain of musculoskeletal symptoms than a control population. Accordingly, we conducted a study to determine whether musculoskeletal symptoms reflected observable physical disorder, to ascertain the relationship between symptoms and measures of mood, memory and executive function and to assess any need for future screening. Methods: A 10% random sample of responders to a prior postal health questionnaire was examined (151 divers, 120 non-diving offshore workers). Participants underwent physical examination and a neuropsychological test battery for memory and executive function. Participants also completed the Hospital Anxiety and Depression Scale for anxiety (HADSa) and depression (HADSd), and questionnaires for physical health-related quality of life (SF36 PCS), mental health-related quality of life (SF36 MCS), memory (Cognitive Failures Questionnaire (CFQ), Prospective and Retrospective Memory Questionnaire (PRMQ)), executive function (dysexecutive syndrome questionnaire (DEX)), musculoskeletal symptoms (MSS) and general unrelated symptom reporting. Results: Of participants with moderate/severe musculoskeletal symptoms, 52% had physical signs, and of participants with no symptoms, 73% had no physical signs. There was no difference in the prevalence of signs or symptoms between groups. Musculoskeletal symptoms were associated with lower SF36 PCS for both groups. In divers, musculoskeletal symptoms were associated with higher general unrelated symptom reporting and poorer scoring for HADSa, PRMQ, CFQ and DEX with scores remaining within the normative range. A positive physical examination was associated with general unrelated symptom reporting in divers. There were no differences in neuropsychological test scores attributable to either group or musculoskeletal symptoms. Conclusions: Musculoskeletal symptoms were associated with physical signs, but this was not a strong effect. Reporting of musculoskeletal symptoms by the divers studied was also associated with a tendency to report symptoms generally or somatisation, and caution should be exercised regarding their interpretation as an indication of physical disease or their use for health screening

Search for transient optical counterparts to high-energy IceCube neutrinos with Pan-STARRS1

In order to identify the sources of the observed diffuse high-energy neutrino flux, it is crucial to discover their electromagnetic counterparts. IceCube began releasing alerts for single high-energy ($E > 60$ TeV) neutrino detections with sky localisation regions of order 1 deg radius in 2016. We used Pan-STARRS1 to follow-up five of these alerts during 2016-2017 to search for any optical transients that may be related to the neutrinos. Typically 10-20 faint ($m < 22.5$ mag) extragalactic transients are found within the Pan-STARRS1 footprints and are generally consistent with being unrelated field supernovae (SNe) and AGN. We looked for unusual properties of the detected transients, such as temporal coincidence of explosion epoch with the IceCube timestamp. We found only one transient that had properties worthy of a specific follow-up. In the Pan-STARRS1 imaging for IceCube-160427A (probability to be of astrophysical origin of $\sim$50 %), we found a SN PS16cgx, located at 10.0' from the nominal IceCube direction. Spectroscopic observations of PS16cgx showed that it was an H-poor SN at z = 0.2895. The spectra and light curve resemble some high-energy Type Ic SNe, raising the possibility of a jet driven SN with an explosion epoch temporally coincident with the neutrino detection. However, distinguishing Type Ia and Type Ic SNe at this redshift is notoriously difficult. Based on all available data we conclude that the transient is more likely to be a Type Ia with relatively weak SiII absorption and a fairly normal rest-frame r-band light curve. If, as predicted, there is no high-energy neutrino emission from Type Ia SNe, then PS16cgx must be a random coincidence, and unrelated to the IceCube-160427A. We find no other plausible optical transient for any of the five IceCube events observed down to a 5$\sigma$ limiting magnitude of $m \sim 22$ mag, between 1 day and 25 days after detection.Comment: 20 pages, 6 figures, accepted to A&

Neutrinos below 100 TeV from the southern sky employing refined veto techniques to IceCube data

Many Galactic sources of gamma rays, such as supernova remnants, are expected to produce neutrinos with a typical energy cutoff well below 100 TeV. For the IceCube Neutrino Observatory located at the South Pole, the southern sky, containing the inner part of the Galactic plane and the Galactic Center, is a particularly challenging region at these energies, because of the large background of atmospheric muons. In this paper, we present recent advancements in data selection strategies for track-like muon neutrino events with energies below 100 TeV from the southern sky. The strategies utilize the outer detector regions as veto and features of the signal pattern to reduce the background of atmospheric muons to a level which, for the first time, allows IceCube searching for point-like sources of neutrinos in the southern sky at energies between 100 GeV and several TeV in the muon neutrino charged current channel. No significant clustering of neutrinos above background expectation was observed in four years of data recorded with the completed IceCube detector. Upper limits on the neutrino flux for a number of spectral hypotheses are reported for a list of astrophysical objects in the southern hemisphere.Comment: 19 pages, 17 figures, 2 table

Do gastrointestinal complaints increase the risk for subsequent medically certified long-term sickness absence? The HUSK study

<p>Abstract</p> <p>Background</p> <p>Gastrointestinal complaints are very common in the general population and very often co-occur with common mental disorders. We aimed to study the prospective impact of gastrointestinal complaints on long term sickness absence, and address the contribution from co-occurring common mental disorders and other somatic symptoms.</p> <p>Method</p> <p>Health data on 13 880 40-45 year olds from the Hordaland Health Study (1997-99) were linked to national registries on sickness absence. As part of a wider health screening, gastrointestinal complaints were ascertained. Participant's anxiety and depression, and the presence of other somatic symptoms were evaluated. In Cox regression models, we predicted sickness absences over an average 5.4 years follow-up, with adjustment for confounders, anxiety and depression and other somatic symptoms.</p> <p>Results</p> <p>After adjusting for gender, level of education and smoking, those reporting GI complaints had higher risk for later sickness absence (HR = 1.42, 95% CI 1.34-1.51). GI complaints were associated with both anxiety (OR = 3.66, 95% CI 3.31-4.04) and depression (OR = 3.28, 95% CI 2.89-3.72), and a high level of other somatic symptoms (OR = 8.50, 95% CI 7.69-9.40). The association of GI complaints was still independently associated with future sickness absence (HR = 1.17, 95% CI 1.10-1.16) adjusting for mental illness and other somatic symptoms.</p> <p>Discussion</p> <p>Sickness absence is a complex behavioural outcome, but our results suggest GI complaints contribute by increasing the risk of long term sickness absence independently of comorbid mental illness and presence of other somatic symptoms. Occupational consequences of illness are important, and should also be addressed clinically with patients presenting with GI complaints.</p

Sick-listed employees with severe medically unexplained physical symptoms: burden or routine for the occupational health physician? A cross sectional study

Background: The two primary objectives of this study were to the assess consultation load of occupational health physicians (OHPs), and their difficulties and needs with regard to their sickness certification tasks in sick-listed employees with severe medical unexplained physical symptoms (MUPS). Third objective was to determine which disease-, patient-, doctor- and practice-related factors are associated with the difficulties and needs of the OHPs. Methods: In this cross-sectional study, 43 participating OHPs from 5 group practices assessed 489 sick-listed employees with and without severe MUPS. The OHPs filled in a questionnaire about difficulties concerning sickness certification tasks, consultation time, their needs with regard to consultation with or referral to a psychiatrist or psychologist, and communication with GPs. The OHPs also completed a questionnaire about their personal characteristics. Results: OHPs only experienced task difficulties in employees with severe MUPS in relation to their communication with the treating physician. This only occured in cases in which the OHP attributed the physical symptoms to somatoform causes. If they attributed the physical symptoms to mental causes, the OHPs reported a need to consultate a psychiatrist about the diagnosis and treatment. Conclusions: OHPs experience few difficulties with their sickness certification tasks and consultation load concerning employees with severe MUPS. However, they encounter problems if the diagnostic uncertainties of the treating physician interfere with the return to work process. OHPs have a need for psychiatric expertise whenever they are uncertain about the psychiatric causes of a delayed return to work process. We recommend further training programs for OHPs. They should also have more opportunity for consultation and referral to a psychiatrist, and their communication with treating physicians should be improved