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Reliable forecast of COVID-19 hospital admissions in near-term horizons can help enable effective resource management which is vital in reducing pressure from healthcare services. The use of mobile network data has come to attention in response to COVID-19 pandemic leveraged on their ability in capturing people social behavior. Crucially, we show that there are latent features in irreversibly anonymized and aggregated mobile network data that carry useful information in relation to the spread of SARS-CoV-2 virus. We describe development of the forecast models using such features for prediction of COVID-19 hospital admissions in near-term horizons (21 days). In a case study, we verified the approach for two hospitals in Sweden, Sahlgrenska University Hospital and Södra Älvsborgs Hospital, working closely with the experts engaged in the hospital resource planning. Importantly, the results of the forecast models were used in year 2021 by logisticians at the hospitals as one of the main inputs for their decisions regarding resource management., (© 2022. The Author(s).)

The maritime expansion of Scandinavian populations during the Viking Age (about AD 750-1050) was a far-flung transformation in world history 1,2 . Here we sequenced the genomes of 442 humans from archaeological sites across Europe and Greenland (to a median depth of about 1×) to understand the global influence of this expansion. We find the Viking period involved gene flow into Scandinavia from the south and east. We observe genetic structure within Scandinavia, with diversity hotspots in the south and restricted gene flow within Scandinavia. We find evidence for a major influx of Danish ancestry into England; a Swedish influx into the Baltic; and Norwegian influx into Ireland, Iceland and Greenland. Additionally, we see substantial ancestry from elsewhere in Europe entering Scandinavia during the Viking Age. Our ancient DNA analysis also revealed that a Viking expedition included close family members. By comparing with modern populations, we find that pigmentation-associated loci have undergone strong population differentiation during the past millennium, and trace positively selected loci-including the lactase-persistence allele of LCT and alleles of ANKA that are associated with the immune response-in detail. We conclude that the Viking diaspora was characterized by substantial transregional engagement: distinct populations influenced the genomic makeup of different regions of Europe, and Scandinavia experienced increased contact with the rest of the continent.

Autoimmune polyendocrine syndrome type 1 (APS1) is a monogenic disorder that features multiple autoimmune disease manifestations. It is caused by mutations in the Autoimmune regulator (AIRE) gene, which promote thymic display of thousands of peripheral tissue antigens in a process critical for establishing central immune tolerance. We here used proteome arrays to perform a comprehensive study of autoimmune targets in APS1. Interrogation of established autoantigens revealed highly reliable detection of autoantibodies, and by exploring the full panel of more than 9000 proteins we further identified MAGEB2 and PDILT as novel major autoantigens in APS1. Our proteome-wide assessment revealed a marked enrichment for tissue-specific immune targets, mirroring AIRE's selectiveness for this category of genes. Our findings also suggest that only a very limited portion of the proteome becomes targeted by the immune system in APS1, which contrasts the broad defect of thymic presentation associated with AIRE-deficiency and raises novel questions what other factors are needed for break of tolerance.

We measured bone mineral density (BMD) with dual-energy X-ray absorptiometry in the total body, at the lumbar spine, at the femoral neck and in the total hip, in 18 young adults with a median of 18.2 years after SCT. Fifteen patients had undergone auto-SCT and all patients had received TBI. The patients had significantly lower BMD in the total body, at the femoral neck, and in the total hip compared with age- and sex-matched controls. Six of 18 patients (33%) had low bone mass (z-score <-1) at one or more measurement sites, as opposed to two of the controls (11%, P=0.29). We found no significant influence of growth hormone levels or of untreated hypogonadism on BMD variables. Levels of 25-hydroxy (25(OH)) vitamin D were lower among the patients (35.2 vs 48.8 nmol/L, P=0.044) and were significantly correlated with total body BMD in the patient group (r=0.55, P=0.021). All six patients with low bone mass had hypovitaminosis D (≤37 nmol/L as opposed to 4 of the 11 (36%) patients without low bone mass (P=0.035). In conclusion, we found decreased BMD in SCT survivors, which may in part be caused by 25(OH) vitamin D deficiency.

After SCT in childhood, survivors may develop disorders of glucose metabolism. The role of obesity is controversial. We measured insulin sensitivity using the homeostasis model assessment (HOMA) and the frequently sampled i.v. glucose tolerance test (FSIVGTT), as well as body composition using dual-energy X-ray absorptiometry in 18 young adults median 18.2 years after SCT and compared them with matched controls. We also measured growth hormone (GH) secretion, and levels of leptin and adiponectin. HOMA showed insulin resistance in eight patients (44%), as opposed to none of the controls (P=0.008) and FSIVGTT showed a decreased sensitivity index in the patients (2.98 vs 4.54 mU/L/min, P=0.042). Dual energy X-ray absorptiometry showed a higher percentage fat mass in the patients (34.9 vs 24.3%, P=0.011), which correlated inversely with the sensitivity index (r=-0.52, P=0.032). The patients had a lower peak value of GH (GH(max) 9 vs 20.7 mU/L, P=0.002). Time post SCT correlated with percentage fat mass and inversely with GH(max). The patients had higher levels of leptin and lower levels of adiponectin, even after adjustment for fat mass. We propose that the decreased insulin sensitivity may primarily be explained by the adverse body composition, which may owe to long-standing GH deficiency.

We describe pubertal development and growth in 17 children who underwent bone marrow transplantation (BMT), including total body irradiation (TBI) for ALL. Seven children also received cranial irradiation (CI) and five boys testicular irradiation. All underwent transplantation before (n=15) or at the beginning of (n=2) puberty and reached a final height (FH). Puberty started spontaneously in all boys not given testicular irradiation. All boys who received testicular irradiation developed hypergonadotrophic hypogonadism. Puberty started spontaneously in two girls and was induced with increasing doses of ethinylestradiol in two girls. In two girls, a low dose of ethinylestradiol was given until menarche. In one girl with early onset of puberty and short stature, puberty was blocked with a GnRH analogue. The standard deviation score for height decreased significantly from BMT to FH, both in the children who received TBI only (-1.1, P=0.005) as well as in those given additional CI (-1.7, P=0.027). Most of the loss occurred during puberty. In all, 10 children received growth hormone (GH) treatment. CI, young age at BMT, and short duration of GH treatment were predictors of height loss after BMT. Although limited by the small and heterogeneous sample, our study supports the use of early GH treatment in children with decelerating growth rate and low GH levels.

Apnea occurs commonly in preterm infants. Theophylline is used as prophylaxis and treatment. Apart from improving ventilatory function, theophylline may also have metabolic effects, including an effect on glucose metabolism and lipolysis. No data are available on the effect of theophylline on glucose production and lipolysis in preterm infants at start of medication. Ten preterm infants with gestational ages of < or = 32 wk, postnatal ages of 16-84 h, and birth weights > 900 g were recruited. Hepatic glucose production and lipolysis were measured by use of gas chromatography/mass spectrometry after constant rate infusion of [6,6-2H2]glucose and [2-13C]glycerol tracers. Plasma glucose levels increased after theophylline administration (mean +/- SD, 4.0 +/- 1.9 mmol/L before and 4.7 +/- 2.1 mmol/L after start of therapy), whereas the rate of glucose production decreased (6.0 +/- 2.5 mg.kg-1.min-1 and 4.3 +/- 1.9 mg.kg-1.min-1, respectively). The plasma glycerol concentration did not show any change after theophylline administration (154 +/- 257 mumol/L before and 217 +/- 258 mumol/L after), and the same was true for the rate of glycerol production (5.9 +/- 2.6 mumol.kg-1.min-1 before and 6.7 +/- 3.0 mumol.kg-1.min-1 after). The fraction of glycerol converted into glucose did not change significantly, although the percentage of glucose derived from glycerol increased after theophylline administration. The results are in line with the lack of adverse metabolic effects at start of theophylline treatment in the preterm infant.

In infants of diabetic mothers, maternal-fetal hyperglycemia induces fetal hyperinsulinemia, which may be sustained for several hours after birth. The inhibitory effect of insulin on glycogenolysis, gluconeogenesis, and lipolysis increases the risk of hypoglycemia in these infants. Eight term infants of diabetic mothers were studied between 3.9 and 8.5 h postnatally. The maternal diabetes was considered well controlled as judged by self-monitoring of blood glucose and Hb Alc. Neonatal plasma concentrations of glucose, glycerol, and insulin were monitored and averaged 2.7 +/- 0.7 mM, 371 +/- 116 microM, and 15.9 +/- 2.8 microU.mL-1, respectively. Stable isotope-gas chromatography/ mass spectrometry techniques were used to determine glucose and glycerol turnover rates and gluconeogenesis from glycerol in the infants. The appearance rates of glucose and glycerol averaged 20.0 +/- 5.4 mumol.kg-1.min-1 (3.6 +/- 1.0 mg.kg-1.min-1), and 8.9 +/- 2.3 mumol.kg-1.min-1, respectively. The fraction of glycerol appearance rate converted to glucose was 68.2 +/- 17.3%, which accounted for 15.5 +/- 4.6% of glucose production. Thus, compared with healthy term infants studied previously under identical conditions, the infants of diabetic mothers had higher insulin concentrations and attenuated glucose production. Despite increased insulin concentrations, lipolysis was unimpaired, and the gluconeogenic contribution from glycerol was higher than in the healthy newborns.

Extremely preterm infants have been shown capable of producing glucose at a rate comparable to that of term infants, but virtually no data are available on their capacity for lipolysis and gluconeogenesis. To address this issue, we studied the flux of glycerol and its gluconeogenic contribution to hepatic glucose output by determining the endogenous plasma appearance rate of glycerol (glycerol Ra) and its conversion to glucose in 10 newborn infants, 24-27 wk of gestational age. The study was performed during the 1st d of life by tracer dilution technique using [6,6-2H2]glucose and [2-13C]glycerol given as constant rate i.v. infusions. Plasma isotopic enrichments of the tracers were obtained by gas chromatography/mass spectrometry. Endogenous glycerol Ra ranged from 2.4 to 21.6 (median 5.0) mumol.kg-1.min-1, of which 31.5% (25.6-64.4%) was converted to glucose. The glucose production rate averaged 17.5 +/- 5.4 mumol.kg-1.min-1 (3.2 +/- 1.0 mg.kg-1.min-1), of which 5.0% (1.6-37.6%) was derived from glycerol. The results show that extremely preterm infants, despite limited fat stores, are capable of generating glycerol at a rate within the range reported for term and near term newborns. The infants were also capable of converting part of this glycerol to glucose, providing a contribution to hepatic glucose production comparable to that found in more mature newborns.

Small substrate stores and immature enzyme systems make preterm infants prone to develop hypoglycemia. Hyperglycemia may also occur, particularly when these infants are given i.v. glucose. To evaluate the capacity for regulation of glucose production in response to glucose infusion, 10 newborn infants, born after 25-30 wk of gestation, were studied. Their glucose production rates (GPR) were calculated and the concentrations of glucose, insulin, and glucagon in plasma were measured during infusion of glucose at a rate of first 1.7 +/- 0.2 and then 6.5 +/- 0.3 mg.kg-1.min-1 (9.4 +/- 1.1 and 36.1 +/- 1.7 mumol.kg-1.min-1) (mean +/- SD). GPR was determined by use of D-6,6-2H2-glucose. When the rate of infusion of glucose was increased, GPR decreased from 4.3 +/- 1.3 to 1.4 +/- 1.1 mg.kg-1.min-1 (23.9 +/- 7.2 to 7.8 +/- 6.1 mumol.kg-1.min-1) (mean +/- SD) (p = 0.00006). In addition, the plasma insulin concentration increased from 6 +/- 2 to 11 +/- 4 microU.mL-1 (p = 0.006) and the plasma glucose concentration from 3.6 +/- 1.1 to 6.1 +/- 1.3 mM (mean +/- SD) (p = 0.0002), whereas the glucagon concentration remained unchanged. Only the insulin concentration in plasma was significantly related to GPR. The results show that very immature newborn infants have an incomplete and varying capacity to respond to glucose infusion with suppression of glucose production. Insulin seems to be more important than plasma glucose in the regulation of glucose homeostasis in these infants.

Neonatal hypoglycemia is a frequent complication in immature infants. This may be due to small substrate stores, a high brain:body weight ratio, and immature enzyme systems. The purpose of the present study was to investigate the rate of glucose production in newborn infants with gestational ages of less than 28 wk. The subjects were 10 newborn infants delivered after 25 to 26 gestational wk. Their mean birth weight was 772 g (range 588-1000 g), and their mean postnatal age at the time of the study was 15 h (range 4-24 h). An isotopic compound (D-6,6-2H2-glucose) was given as a constant-rate i.v. infusion. In addition to dideuteroglucose, eight of the infants also received an i.v. infusion of unlabeled glucose at a rate of 1.4-2.6 mg.kg-1.min-1. Blood samples for determination of the concentration and isotopic enrichment of plasma glucose were obtained every 15 min in a 2-h period. Isotopic enrichment, measured by gas chromatography/mass spectrometry, was used for calculating the glucose production rate. The mean glucose production rate related to body weight (+/- SD) was 6.1 +/- 1.5 mg.kg-1.min-1. The results show that infants born at < 28 gestational wk have a capacity to produce glucose on their 1st d of life at rates close to or even exceeding those reported in term infants.

Infantile Zellweger syndrome belongs to the group of peroxisomal disorders that lack peroxisomes. Both trihydroxycoprostanic acid (THCA), the precursor to cholic acid, and dihydroxycoprostanic acid (DHCA), the precursor to chenodeoxycholic acid, accumulate in this disease. In previous studies, we have shown that liver peroxisomes are required for the conversion of THCA into cholic acid both in vitro and in vivo by measuring a defective conversion in infants with Zellweger syndrome. In our present study, the conversion of DHCA into chenodeoxycholic acid has been measured in an infant with Zellweger syndrome to evaluate the importance of liver peroxisomes for the formation of chenodeoxycholic acid. Coprostanic acidemia was present from the second day of life with high levels of THCA and only trace amounts of DHCA. The conversion of i.v. administered [3H]DHCA into chenodeoxycholic acid was only 7% compared with the 80% conversion in an analogous study in an adult. There was, however, a rapid incorporation of 3H into biliary THCA and, after a lag phase, the 3H was incorporated into biliary cholic acid. After 72 h, 15% of [3H]DHCA was converted to cholic acid. The pool size of DHCA was 1.2 mg/m2 and the pool size of both cholic acid and chenodeoxycholic acid was markedly reduced. The renal excretion of cholic acid was more efficient than that of the less polar chenodeoxycholic acid. More polar metabolites of DHCA and THCA are formed in alternative metabolic pathways facilitating renal excretion of these toxic intermediates. We conclude that liver peroxisomes are essential for a normal conversion of DHCA into chenodeoxycholic acid.

The metabolism of [24-14C]lithocholic acid was studied in the microsomal fraction of fetal human liver homogenates. Fetal livers were obtained at legal abortions performed between wk 14 and 24. Product formation was analyzed by thin-layer chromatography, liquid chromatography, and gas chromatography-mass spectrometry. From wk 14 lithocholic acid was hydroxylated in several positions. Hyodeoxycholic acid (3 alpha,6 alpha-dihydroxy-5 beta-cholanoic) and 1 beta,3 alpha-dihydroxy-5 beta-cholanoic acid were identified among the products. The 3 beta-isomer of the former acid, 6 alpha-hydroxy-3-oxo-5 beta-cholanoic acid and a 2-hydroxylithocholic acid were tentatively identified. Two other metabolites carried a hydroxyl group in an unknown position, one of them probably at an angular methyl group. The highest total conversions per mg of microsomal protein were obtained with preparations from 18 wk fetuses. The results are discussed with particular reference to the role of lithocholic acid in fetal hepatotoxicity.