Onset and transition of and recovery from adverse development:study methodology

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential. METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions. RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD

Stabilization of angiotensin-(1-7) by key substitution with a cyclic non-natural amino acid

Angiotensin-(1-7) [Ang-(1-7)], a heptapeptide hormone of the renin-angiotensin-aldosterone system (RAAS), is a promising candidate as a treatment for cancer that reflects its antiproliferative and anti-angiogenic properties. However, the peptide’s therapeutic potential is limited by the short half-life and low bioavailability resulting from rapid enzymatic metabolism by peptidases including angiotensin-converting enzyme (ACE) and dipeptidyl peptidase 3 (DPP 3). We report the facile assembly of three novel Ang-(1-7) analogues by solid-phase peptide synthesis which incorporates the cyclic non-natural δ-amino acid ACCA. The analogues containing the ACCA substitution at the site of ACE cleavage exhibit complete resistance to human ACE, while substitution at the DDP3 cleavage site provided stability against DPP 3 hydrolysis. Furthermore, the analogues retain the anti-proliferative properties of Ang-(1-7) against the 4T1 and HT-1080 cancer cell lines. These results suggest that ACCA-substituted Ang-(1-7) analogues which show resistance against proteolytic degradation by peptidases known to hydrolyze the native heptapeptide may be novel therapeutics in the treatment of cancer

Correlation between driving-related skill and alcohol use in young-adults from six European countries: the TEN-D by Night Project

<p>Abstract</p> <p>Background</p> <p>Only few studies with small experimental samples investigated the impact of psychoactive substances on driving performance. We conducted a multicenter international cross-sectional study to evaluate the correlation between alcohol use and driving-related skill as measured by brake reaction time (RT).</p> <p>Methods</p> <p>Before and after the entrance into randomly selected recreational sites from six European countries, all subjects aged 16-35 years, owning a driver license, were asked to compile a structured socio-demographic questionnaire and measure RT (SimuNomad3 driving simulator), breath alcohol concentration (BAC; Drager Alcoltest), and drug use (Oratect III saliva test, only at the exit). Mixed regression modeling was used to evaluate the independent association between RT and alcohol concentration or drug use.</p> <p>Results</p> <p>Before the entrance into the recreational site, 4534 subjects completed all assessments and composed the final sample. Their mean age was 23.1 ± 4.2y; 68.3% were males; 54.7% had BAC > 0 g/L (assumed alcoholics); 7.5% declared illegal drug assumption (mostly cannabis). After the exit, 3019 also completed the second assessment: 71.7% showed BAC > 0 g/L. Controlling for age, gender, educational level, occupation, driver license years, and drug use, BAC was positively associated with RT, achieving significance, however, only when BAC was higher than 0.49 g/L. Significant interaction terms were found between BAC and female gender or drug use, with highest RTs (> 1 sec.) recorded among drug users with BAC > = 1 g/L.</p> <p>Conclusions</p> <p>This field study confirms previous experimental data on the negative impact of alcohol use on driving-related skill, supporting regulations and educational campaigns aimed at discouraging driving after consumption of psychoactive substances.</p

The Dark Energy Survey : more than dark energy – an overview

This overview paper describes the legacy prospect and discovery potential of the Dark Energy Survey (DES) beyond cosmological studies, illustrating it with examples from the DES early data. DES is using a wide-field camera (DECam) on the 4 m Blanco Telescope in Chile to image 5000 sq deg of the sky in five filters (grizY). By its completion, the survey is expected to have generated a catalogue of 300 million galaxies with photometric redshifts and 100 million stars. In addition, a time-domain survey search over 27 sq deg is expected to yield a sample of thousands of Type Ia supernovae and other transients. The main goals of DES are to characterize dark energy and dark matter, and to test alternative models of gravity; these goals will be pursued by studying large-scale structure, cluster counts, weak gravitational lensing and Type Ia supernovae. However, DES also provides a rich data set which allows us to study many other aspects of astrophysics. In this paper, we focus on additional science with DES, emphasizing areas where the survey makes a difference with respect to other current surveys. The paper illustrates, using early data (from ‘Science Verification’, and from the first, second and third seasons of observations), what DES can tell us about the Solar system, the Milky Way, galaxy evolution, quasars and other topics. In addition, we show that if the cosmological model is assumed to be +cold dark matter, then important astrophysics can be deduced from the primary DES probes. Highlights from DES early data include the discovery of 34 trans-Neptunian objects, 17 dwarf satellites of the Milky Way, one published z > 6 quasar (and more confirmed) and two published superluminous supernovae (and more confirmed)

End-Stage Renal Disease Among HIV-Infected Adults in North America

Background. Human immunodeficiency virus (HIV)-infected adults, particularly those of black race, are at high-risk for end-stage renal disease (ESRD), but contributing factors are evolving. We hypothesized that improvements in HIV treatment have led to declines in risk of ESRD, particularly among HIV-infected blacks

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Den svårfångade motionären : En studie avseende etablerandet av regelbundna motionsvanor

The purpose of this descriptive study is to examine and describe the process of establishing regular physical exercising habits in the form of jogging, and in the context of this process, to describe the hindrance factors that stand in the way of establishing such habits; also to describe the effects and experiences, in a wide sense, of recurrent physical activities and how these effects change over time. A second purpose is to look more closely at the factors that influence the situation for women who want to take up regular physical training habits. 44 men and women (22 of each sex) in the age-span of 30-50 years, who were then physically non-active, became the subjects of the study. The observations were made during a period of 24 months, and the subjects were to jog not less then 3 times per every 2 weeks during the 24-month period. The results show, that during the first few months,various kinds of hindrance anei difficulties dominate the picture; this is particularly true of the women joggers. After the 24 months, most obstacles were overcome, with the exception of one, typical of the women joggers, namely fear of being assaulted while jogging. Initially, the experiences while jogging were both positive and negative, but over time there was a change towards predominantly positive experiences. As regards aerobic work capacity, there was a general improvement during the first three months; after that the upwards movement levelled out. The mental effects vere initially of a short-range nature, whereas the long-range effects appeared later and increased steadily during the whole 24-month period. The motives for beginning to take regular phyical exercises and the motives for continuing to do so are qualitatively different. The former are often based on external/instrumental motivation, whereas the latter are of an internal nature. Furthermore, it may be noted that men and women live in different worlds even with respect to jogging. Obstacles and problems are different as well as experiences and effects.Syftet med föreliggande deskriptiva studie har varit att studera och beskriva utvecklingsförloppet med avseende på processen etablerandet av regelbundna motionsvanor, i form av jogging, och, som en del därav, beskriva hinder och svårigheter i samband med motionsutövande samt upplevelser och effekter i vid bemärkelse av regelbunden fysisk aktivitet samt deras förändring över tid. Ett delsyfte har varit att särskilt studera kvinnors villkor och möjligheter för motionsutövande. Fyrtiofyra tidigare fysiskt inaktiva personer i åldern 30-50 år, lika många män och kvinnor, deltog i försöket som pågick under 24 månader och som innebar att deltagarna skulle utöva jogging minst 3ggr/14 dagar under tidsperioden. Resultaten visar att under de första månaderna dominerar hindren och svårigheterna inför motionsutövandet; i synnerhet gäller detta kvinnorna. Efter två års tid har de flesta barriärer övervunnits, frånsett ett hinder som är enbart kvinnligt, nämligen rädsla för antastanden under joggingen. Upplevelserna under joggingutö-vandet är i initialskedet lika ofta negativa som positiva och förändras över tid åt det positiva hållet. Effekterna är inledningsvis främst av fysisk/fysiologisk karaktär. Vad gäller ökning av syreupptagningsförmåga sker i stort sett hela förbättringen under de tre första månaderna; därefter planar kurvan ut. De psykiska effekterna är i början kortsiktiga, medan de långsiktiga psykiska effekterna inträder senare och ökar successivt i omfattning under hela försöksperioden. Motiven för att börja och motiven för att fortsätta motionera är kvalitativt olika, på så sätt att motiven för att börja ofta har sin grund i yttre motivation medan motiven för att fortsätta är inifrån kommande. Vidare kan konstateras att kvinnors och män världar ser olika ut också i motionshänseende. Detta gäller såväl hinder och problem som upplevelser och effekter av motionsutövande.digitalisering@um