Elevated fetal steroidogenic activity in autism

Autism affects males more than females, giving rise to the idea that the influence of steroid hormones on early fetal brain development may be one important early biological risk factor. Utilizing the Danish Historic Birth Cohort and Danish Psychiatric Central Register, we identified all amniotic fluid samples of males born between 1993 and 1999 who later received ICD-10 (International Classification of Diseases, 10th Revision) diagnoses of autism, Asperger syndrome or PDD-NOS (pervasive developmental disorder not otherwise specified) (n=128) compared with matched typically developing controls. Concentration levels of Δ4 sex steroids (progesterone, 17α-hydroxy-progesterone, androstenedione and testosterone) and cortisol were measured with liquid chromatography tandem mass spectrometry. All hormones were positively associated with each other and principal component analysis confirmed that one generalized latent steroidogenic factor was driving much of the variation in the data. The autism group showed elevations across all hormones on this latent generalized steroidogenic factor (Cohen's d=0.37, P=0.0009) and this elevation was uniform across ICD-10 diagnostic label. These results provide the first direct evidence of elevated fetal steroidogenic activity in autism. Such elevations may be important as epigenetic fetal programming mechanisms and may interact with other important pathophysiological factors in autism

Fault Detection and Diagnosis Encyclopedia for Building Systems:A Systematic Review

This review aims to provide an up-to-date, comprehensive, and systematic summary of fault detection and diagnosis (FDD) in building systems. The latter was performed through a defined systematic methodology with the final selection of 221 studies. This review provides insights into four topics: (1) glossary framework of the FDD processes; (2) a classification scheme using energy system terminologies as the starting point; (3) the data, code, and performance evaluation metrics used in the reviewed literature; and (4) future research outlooks. FDD is a known and well-developed field in the aerospace, energy, and automotive sector. Nevertheless, this study found that FDD for building systems is still at an early stage worldwide. This was evident through the ongoing development of algorithms for detecting and diagnosing faults in building systems and the inconsistent use of the terminologies and definitions. In addition, there was an apparent lack of data statements in the reviewed articles, which compromised the reproducibility, and thus the practical development in this field. Furthermore, as data drove the research activity, the found dataset repositories and open code are also presented in this review. Finally, all data and documentation presented in this review are open and available in a GitHub repository

Primiparous women differ from multiparous women after early discharge regarding breastfeeding, anxiety, and insecurity:A prospective cohort study

INTRODUCTION: Breastfeeding and factors influencing breastfeeding are essential when considering the association between parity and neonatal and maternal morbidity risks when mothers are discharged within 24 hours after birth. However, there is a lack of studies examining the effect of parity and breastfeeding in a setting where all healthy mothers are recommended discharge four hours after birth. Therefore, this study examined the association between parity and the time for discharge, breastfeeding, and factors influencing breastfeeding. METHODS: The study was designed as a prospective cohort study. Data were obtained from questionnaires at one and at six weeks after birth, and combined with registered data. All 147 included mothers were healthy, with an uncomplicated birth and a healthy newborn, discharged within 24 hours after birth. RESULTS: This study documented that primiparous women had a higher relative risk (RR=2.62; 95% CI: 1.35–5.10) of having doubts about infant feeding after discharge than multiparous women. Furthermore, 54% of primiparous women contacted the maternity ward after discharge compared to 27% of multiparous women. Twice as many primiparous than multiparous women felt anxious or depressed at one and at six weeks after birth. Finally, the study documented that 13% of primiparous women and 5% of multiparous women discharged within six hours after birth perceived the time before discharge to be too short. CONCLUSIONS: Primiparous women differ from multiparous women regarding breastfeeding, insecurity, and anxiety. Special attention towards primiparous women and a follow-up strategy that allows the mothers to contact the maternity ward after early discharge is recommended

Multiple Input Electrode Gap Control During Vacuum Arc Remelting

Accurate control of the electrode gap in a vacuum arc remelting (VAR) furnace has been a goal of melters for many years. The size of the electrode gap has a direct influence on ingot solidification structure. At the high melting currents (30 to 40 kA) typically used for VAR of segregation insensitive Ti and Zr alloys, process voltage is used as an indicator of electrode gap, whereas drip-short frequency (or period) is usually used at the lower currents (5 to 8 kA) employed during VAR of superalloys. Modem controllers adjust electrode position or drive velocity to maintain a voltage or drip-short frequency (or period) set-point. Because these responses are non-linear functions of electrode gap and melting current, these controllers have a limited range for which the feedback gains are valid. Models are available that relate process voltage and drip-short frequency to electrode gap. These relationships may be used to linearize the controller feedback signal. An estimate of electrode gap may then be obtained by forming a weighted sum of the independent gap estimates obtained from the voltage and drip-short signals. By using multiple independent measures to estimate the gap, a controller that is less susceptible to process disturbances can be developed. Such a controller was designed, built and tested. The tests were carried out at Allvac Corporation during VAR of 12Cr steel at intermediate current levels

Psychotropic drug use following venous thromboembolism versus diabetes mellitus in adolescence or young adulthood: A Danish nationwide cohort study

© Author(s) (or their employer(s)) 2018. Objectives Critical and chronic illness in youth such as diabetes can lead to impaired mental health. Despite the potentially traumatic and life-Threatening nature of venous thromboembolism (VTE), the long-Term mental health of adolescents and young adults with VTE is unclear. We compared the long-Term mental health of adolescents and young adults with VTE versus adolescents and young adults with insulin-dependent diabetes mellitus (IDDM) using psychotropic drug purchase as proxy for mental health. Design Nationwide registry-based cohort study. Setting Denmark 1997-2015. Participants All patients aged 13-33 years with an incident diagnosis of VTE (n=5065) or IDDM (n=6609). Exposure First time primary hospital diagnosis of VTE or IDDM. Primary and secondary outcome measures Adjusted absolute risk and risk difference at 1 and 5 years follow-up for first psychotropic drug purchase comparing patients with VTE and patients with IDDM. Results The absolute 1 year risk of psychotropic drug use was 6.2% among VTE patients versus 3.6% among patients with IDDM, at 5 years this was 19.3%-14.7%, respectively. After adjusting for the effect of sex, age and risk factors for VTE this corresponded to a 1 year risk differences of 1.9% (95 % CI 0.1% to 3.3%). At 5 years follow-up the risk difference was 1.9% (95% CI 0.5% to 3.3%). Conclusion One-fifth of adolescents and young adults with incident VTE had claimed a prescription for a psychotropic drug within 5 years, a risk comparable to that of young patients with IDDM

Efficacy of FODMAP Elimination and Subsequent Blinded Placebo-Controlled Provocations in a Randomised Controlled Study in Patients with Ulcerative Colitis in Remission and Symptoms of Irritable Bowel Syndrome:A Feasibility Study

Background: Patients with inflammatory bowel disease (IBD) and symptoms of irritable bowel syndrome (IBS) may be intolerant to fermentable carbohydrates (FODMAPs). The aim of this study was to test the feasibility of eliminating and subsequently reintroducing FODMAPs in patients with IBS symptoms as part of the IBD manifestation and to compare the severity of IBS symptoms and pain, bloating and quality of life (QoL). Methods: An eight-week randomised open-label FODMAP elimination with double-blinded, crossover provocations of FODMAP and placebo. Diet patients were on a low-FODMAP diet for eight weeks with blinded two-week provocations after two and six weeks. Questionnaires, blood and stool samples were collected. Results: Patient enrolment was challenging. Nineteen participants were included in the study. Eliminating low FODMAP for two weeks resulted in significant decreases in pain and bloating scores (p 0.05). Conclusions: The results document the possibility of performing a randomised controlled study following the gold standard for testing food intolerance with blinding of the Low FODMAP diet. Recruitment of participants was challenging

Integrated safety and efficacy analysis of dasiglucagon for treatment of severe hypoglycaemia in individuals with type 1 diabetes

Aims To perform an integrated analysis of the safety and efficacy of dasiglucagon, a glucagon analogue available in a ready-to-use aqueous formulation, to treat severe hypoglycaemia (SH) in type 1 diabetes (T1D). Materials and Methods An integrated analysis of dasiglucagon safety was conducted on data from two placebo-controlled trials (placebo-controlled pool) and two placebo-controlled and four non-placebo-controlled trials (broad pool) in adults with T1D. An integrated analysis of dasiglucagon efficacy was conducted of pooled data and within demographic subgroups from the two placebo-controlled and two non-placebo-controlled trials in adults with T1D. Results Dasiglucagon had a similar safety and tolerability profile to that of reconstituted glucagon. In the placebo-controlled datasets, no serious adverse events (AEs), AEs leading to withdrawal from the trial, or deaths were reported. The most common causally related AEs were nausea (56.5%) and vomiting (24.6%). The broad pool safety analysis showed similar results. Dasiglucagon efficacy in time to plasma glucose recovery from insulin-induced SH was similar to that of reconstituted glucagon (median 10.0 and 12.0 minutes, respectively) and superior to placebo (median 40.0 minutes; P < 0.0001). The median recovery time was consistent across all placebo-controlled trial subgroups. Conclusions Dasiglucagon was well tolerated and effective as a rapid rescue agent for insulin-induced SH in people with T1D