Synergies of THESEUS with the large facilities of the 2030s and guest observer opportunities.

The proposed THESEUS mission will vastly expand the capabilities to monitor the high-energy sky. It will specifically exploit large samples of gamma-ray bursts to probe the early universe back to the first generation of stars, and to advance multi-messenger astrophysics by detecting and localizing the counterparts of gravitational waves and cosmic neutrino sources. The combination and coordination of these activities with multi-wavelength, multi-messenger facilities expected to be operating in the 2030s will open new avenues of exploration in many areas of astrophysics, cosmology and fundamental physics, thus adding considerable strength to the overall scientific impact of THESEUS and these facilities. We discuss here a number of these powerful synergies and guest observer opportunities.

Reproducibility of the fetal cerebral vessels assessment in full and late term pregnancies.

Objective: Data concerning feasibility of the fetal cerebral Doppler examination in full term and late term pregnancy is lacking. Our purpose was to perform an evaluation of these arteries with power Doppler ultrasound, calculating the percentage of identification and measurement and the intraobserver reproducibility.Methods: This was a cross sectional study evaluating a population of 578 normally grown fetuses divided according to the week of examination. The first group included fetuses examined at week 40 (N = 323) and the second fetuses examined at week 41 (N = 255). The three major branches of the internal carotid artery (anterior, middle and posterior cerebral arteries, ACA, middle cerebral artery (MCA), posterior cerebral arteries (PCA)) and their anastomosis (A1, A2, P1, P2) were examined with power Doppler ultrasonography by three independent ultrasonographers. The proportion of vessel identified and measured was calculated and the reproducibility among the three operators was investigated.Results: The major arteries at the circle of Willis were fully identified/measured in 65/56 and 62/48% of fetuses at 40 and 41 weeks. The MCA obtained the higher percentage of identification and measurement at both periods (> 80 and >70%). The entire set of anastomosis were less frequently identified/measured at both periods (50/< 50% of cases), especially in the A2 segment. The best agreement was obtained in the MCA and the worst in the PCA-P1 segment.Conclusions: At 40 and 41 weeks, the fetal cerebral vessels, especially the MCA, are suitable for power Doppler evaluation, providing an interesting tool to evaluate fetal hemodynamics in full and late term pregnancy.

A Systematic Review of Outcomes and Patient Satisfaction Following Surgical and Non-surgical Treatments for Hair Loss.

INTRODUCTION: This systematic review aims to examine surgical and non-surgical treatments and identify those procedures that are most effective in terms of patient satisfaction. MATERIALS AND METHODS: A systematic review protocol was developed a priori in accordance with the Preferred Reporting for Items for Systematic Reviews and Meta-Analyses-Protocols (PRISMA-P) guidelines. The search was conducted in accordance with the PRISMA guidelines, the Cochrane handbook. A multistep search of the PubMed, MEDLINE, Embase, PreMEDLINE, Ebase, CINAHL, PsycINFO, and Cochrane databases was performed to identify studies on hair loss causes and hair loss treatment with different surgical and non-surgical techniques RESULTS: Our search generated a total of 781 articles; 646 studies were excluded based on the content of the abstracts, and an additional 105 studies were excluded based on the content of the complete article. We performed a review of the 30 remaining studies, which had sufficient data for inclusion, and met all the aforementioned inclusion criteria. Of the 30 studies, four were about minoxidil, four about finasteride, two about dutasteride, three about phototherapy, six about platelet-rich plasma injection, four about follicular unit transplantation technique, six about follicular unit extraction technique, and one about patient satisfaction following surgical treatment without a specified surgical technique. Only three studies used a patient-reported outcome measurement. CONCLUSIONS: Our study is the first comprehensive systematic review of hair loss, looking at the problem from different points of view, and focusing on finding the best solution for the patient. In the literature, there is currently no algorithm for the management of patients who go to a plastic surgeon for a solution to the problem of hair loss. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

[Ultrasonographic and clinical methods in the management of prolonged pregnancy]. / Confronto tra metodiche cliniche e strumentali nella gestione della gravidanza protratta.

AIM: The aim of this study was to evaluate the role of Bishop score, sonographic measurements of uterine cervical length and maternal characteristics, as predictors of spontaneous onset of labor within 24 hours, as well as response to induction in prolonged pregnancies. METHODS: Pregnancies with gestational age over 280 days were followed as outpatient. Patients were included in the study if spontaneous delivery occurred between 286 and 295 days of gestation, or in pregnancies with gestational age of 291-293 days who required labor induction. Data about Bishop score, ultrasonographic cervical characteristics (length, funneling, volume) and maternal features (parity, body mass index and age) registered at the last control immediately before the delivery were retrieved from clinical charts. RESULTS: Data from 195 patients were available. Bishop score and, in particular, ultrasonographic cervical length can predict the spontaneous onset of labor with a positive predictive value (PPV) of 22% and 44%, respectively in 24 hours. On the other hands, in patients requiring labor induction, parity and ultrasonographic cervical length remained the only predictive parameters with a PPV of 39% and 42%, respectively. In term of predictive performance, the value of 30 mm was identified as the best cut-off value for the ultrasonographic cervical length (specificity 59% and sensitivity 69%). CONCLUSION: In prolonged pregnancies, Bishop score and ultrasonographic cervical length were shown to be relevant in the prediction of spontaneous onset of labor, while in patients who required labor induction, ultrasonographic cervical length represented the only clinic parameter predicting the onset of labor.

[Screening of obesity, overweight and thinness in a children population in Rome, Italy]. / Screening per obesità, sovrappeso e sottopeso in una popolazione in età scolare a Roma, Italia.

AIM: Objective of the study was to estimate the prevalence of obesity, overweight and thinness in a children population in Rome, Italy. METHODS: The study sample was created, after informed consent, in a school in Rome, available to the study project. A total of 595 children (289 males, 306 females), aged between 6 to 19 years, underwent following measurements: height and weight, evaluation of body mass index. RESULTS: A normal BMI was recorded in 73.6% of cases. Morbid obesity, obesity, overweight, and thinness grade 1 and 2 prevalence was 1.2%, 4%, 15.3%, 9.2% and 3.8%, respectively, without statistical differences in both genders, except the prevalence of overweight that resulted statistically significant (11.4% females vs. 19.3% males, P<0.05). Differences in the age groups have been found. About 17.2% and 18.7% of children between 7 to 11 years were overweight and obese and about 33.3% and 26.6% between 6 to 8 years thin grade 1 and 2, respectively. CONCLUSION: The study suggests a prevalence of overweight and obesity in our sample lower than that reported in a recent epidemiological survey carried out on Italy. Attention must be taken to underweight, particularly with regard to the most severe form, as a public health problem for all possible risks correlated. In addition, our study shows the involvement of specific age groups. This finding, if confirmed in a larger population, should be associated with a major attention on specific age groups at risk, in order to plan an appropriate treatment program.

[Usefulness of ultrasound in the delivery room]. / Impiego degli ultrasuoni in sala parto.

The use of diagnostic ultrasound and the diffusion of the technique improved the obstetric treatment and the usefulness of ultrasound increases in the delivery room for maternal and fetal care and as method of diagnosis of some obstetric complications. The knowledge of intrapartum ultrasound imaging can be considered useful for the obstetric team, since there is evidence that ultrasound can improve the obstetric management. The mean indications are described: fetal biometry and estimated fetal weight, amniotic fluid volume, fetal situation and presentation, placental localization and anatomy, assessment of size and location of uterine leiomyomas, fetal cardiac activity, evaluation of umbilical cord and fetal cardinal movements intrapartum. Besides, the use of ultrasound is reported in obstetric and postpartum complications. Actually ultrasonography, as a non-invasive, safety and low-cost technique, offers a diagnostic method in particular conditions during labour, delivery and postpartum.

The first case of mitoxantrone exposure in early pregnancy.

Mitoxantrone is an antineoplastic agent considered a potential human teratogen because of its mechanism of action and is classified by the US Food and Drug Administration in pregnancy category risk D. In the literature there are only four cases of women exposed to the drug in late pregnancy. We report the first case of mitoxantrone therapy in the first trimester and during the pregnancy. A 41-year-old woman affected with multiple sclerosis, conceived during therapy and continued mitoxantrone until 29 weeks and 3 days of her pregnancy. She delivered by cesarean section at 39 weeks a growth restricted female baby weighing 1950g without evidence of congenital malformations.

The Von Restorff effect in ageing and Alzheimer's disease.

The purpose of the study was to evaluate the Von Restorff effect in normal ageing and in Alzheimer's disease (AD). A shortened paradigm was administered to three groups of subjects: young volunteers, elderly volunteers and patients with early-stage AD (MMSE>20). Each subject was presented with 25 lists of 10 words each, the target word appearing in double font size. A free recall phase followed the presentation of each list; after completion of the battery, a size recognition test was administered and subjects were inquired regarding the strategy employed and perception of target words. The total number of recalled words differed significantly among the three groups (young volunteers 144.4+/-38.6, elderly volunteers 86.5+/-17.6, patients 44.2+/-14.6). A significant difference in percentage of recall was found between target and non-target words in young (60.0+/-13.8% vs. 45.7%+/-15.0%, p<0.001) and in elderly (31.2+/-11.4% vs. 20.2+/-6.9%, p<0.001) volunteers, but not in patients (10.7+/-6.9% vs. 11.8+/-7.3%). The present study highlights that the Von Restorff effect can be detected in healthy elderly subjects, and that it is significantly reduced in patients in the early stage of AD. On the basis of the findings of the present study it is not possible to disentangle the contribution of visual-perceptual and encoding impairment, both of them potentially contributing to the observed reduction.

Pediatric renal transplantation: 13 years of experience--report from the Chilean Cooperative Multicenter Group.

Between 1989 and 2002, 178 renal transplants were performed in 168 pediatric patients in Chile. The mean age was 10.9 +/- 3.7 years (range 1 to 17.9). End-state renal disease etiologies were: congenital renal hypoplasia/dysplasia, chronic glomerulonephritis, and reflux nephropathy. Seventy received a graft from a living donor (LD), and 108 from a cadaveric donor (CD). Only 9% received antibody induction. Acute rejection episodes were reported in 76 patients: 38% in LD recipients and 48% in CD recipients (P = NS). One-, 3-, and 5-year graft survivals were 88%, 84%, and 76%, respectively, for LD and 86%, 79%, and 68% for CD recipients. Actuarial graft survival was significantly better among those patients with serum creatinine < 1 mg/dL at 1 year posttransplant compared with those with creatinine > 1 mg/dL (P < .05). The graft survival rate has improved from the first period (1989 to 1996) to the second period (1997 to 2002); (P = .05). Patient survival rates at 1, 3, and 5 years were 98%, 98%, and 98%, respectively, for LD, and 95%, 94%, and 94% for CD. Global height/age Z-score decreased from -0.7 at birth to -1.5 when dialysis started, and to -2.4 at the time of transplantation. The Z-score height/age at 1, 3, and 5 years posttransplantation was -2.25, -2.24, and -2.5. No significant differences were observed in transplant outcomes comparing patients younger than 7 years with those older ones. In conclusion, pediatric renal transplant has been performed in Chile with acceptable morbidity. The patient and graft survivals are similar to the reported international experience. In the last period there was a significant improvement in graft survival.

Intra- and interobserver repeatability of femur length measurement in early pregnancy.

OBJECTIVE: To assess the intra- and interobserver reproducibility of songographic measurement of fetal femur length between 10 and 16 weeks of gestation. METHODS: Femur length was measured three times by the same trained observer in each fetus of 136 pregnant women. A second trained observer then repeated the measurements. The coefficient of variation, intraclass correlation coefficient and repeatability coefficient with 95% CIs were calculated for each observer and between the two observers. RESULTS: The inter- and intraobserver repeatabilities of femur length were good. For interobserver correlation, the coefficient of variation was 4.6% (95% CI, 3.0-6.2), the intraclass correlation coefficient was 0.82 (95% CI, 0.69-0.95) and the repeatability coefficient was 2.1 (95% CI, 1.8-2.7). For intraobserver correlation, the coefficient of variation was 4.2% (95% CI, 3.2-5.6), the intraclass correlation coefficient was 0.91 (95% CI, 0.75-0.97) and the repeatability coefficient was 3.23 (95% CI, 2.33-3.86) for Observer 2. Similar results were obtained for the other observer. CONCLUSION: Transvaginal femur length measurement is technically feasible and easy to perform between 10 and 16 weeks of gestation. The high degree of intra- and interobserver repeatability indicates it to be a reproducible method.

Immune response at birth, long-term immune memory and 2 years follow-up after in-utero anti-HBV DNA immunization.

Infections occurring at the end of pregnancy, during birth or by breastfeeding are responsible for the high toll of death among first-week infants. In-utero DNA immunization has demonstrated the effectiveness in inducing specific immunity in newborns. A major contribution to infant immunization would be achieved if a vaccine proved able to be protective as early as at the birth, preventing the typical 'first-week infections'. To establish its potential for use in humans, in-utero DNA vaccination efficiency has to be evaluated for short- and long-term safety, protection at delivery, efficacy of boosts in adults and effective window/s for modulation of immune response during pregnancy, in an animal model suitable with human development. Here we show that a single intramuscular in-utero anti-HBV DNA immunization at two-thirds of pig gestation produces, at birth, antibody titers considered protective in humans. The boost of antibody titers in every animal following recall at 4 and 10 months demonstrates the establishment of immune memory. The safety of in-utero fetus manipulation is guaranteed by short-term (no fetus loss, lack of local alterations, at-term spontaneous delivery, breastfeeding) and long-term (2 years) monitoring. Treatment of fetuses closer to delivery results in immune ignorance without induction of tolerance. This result highlights the repercussion of selecting the appropriate time point when this approach is used to deliver therapeutic genes. All these findings illustrate the relevance of naked DNA-based vaccination technology in therapeutic efforts aimed to prevent the high toll of death among first-week infants.

[Early transvaginal sonographic measurement of cephalic index]. / Misurazione dell'indice cefalico fetale in epoca precoce di gravidanza mediante ecografia transvaginale.

BACKGROUND: The aim of this study is to obtain normal values of cephalic index by transvaginal scan early in pregnancy. METHODS: In this prospective cross-sectional study, transvaginal high-resolution sonography was performed between 57 and 112 days' gestation in 1087 euploid fetuses. Measurements of cephalic index with standard deviations, calculated as the ratio biparietal diameter/occipito-frontal diameter, were obtained in the single gestational periods considered. RESULTS: Cephalic index was found to show fairly constant values throughout the period evaluated with smaller values of standard deviation. The best correlation with gestational age was described by a linear correlation. CONCLUSIONS: The data obtained by transvaginal scan can be used as parameters of normal values in early pregnancy.

[Early transvaginal measurement of cephalic index for the detection of fetuses at risk for Down syndrome]. / L'indice cefalico fetale come marker biometrico nella individuazione in epoca precoce di gravidanza di feti a rischio di trisomia 21.

BACKGROUND: The aim of this study was to evaluate the utility of cephalic index screening in early pregnancy for the identification of fetuses at risk for trisomy 21. METHODS: Measurements of cephalic index, calculated as the ratio between biparietal diameter/occipito-frontal diameter, were obtained in 36 Down syndrome fetuses and the values were compared with normal data in the same gestational periods considered. RESULTS: Cephalic index was found to show fairly constant values throughout the period evaluated. The measurements obtained in Down syndrome fetuses were similar to those obtained in euploid fetuses. CONCLUSIONS: The data obtained show that in early pregnancy cephalic index cannot be considered a useful tool in the detection of fetuses at risk for Down syndrome.

Resting energy expenditure in young patients with cystic fibrosis receiving antibiotic therapy for acute respiratory exacerbations.

BACKGROUND: patients with cystic fibrosis commonly have severe malnutrition and growth retardation. Among possible causes of these manifestations are low caloric intake, loss of nutrients and increased resting energy expenditure. This study was designed to assess the influence of antibiotic therapy for infectious exacerbations on resting energy expenditure in young patients with cystic fibrosis. METHODS: We studied 17 patients with cystic fibrosis (mean age, 13.6 years). All were hospitalized to receive intravenous antibiotic therapy (mean duration, 2 weeks) for acute respiratory exacerbations. At the beginning of therapy and after it ended, all patients underwent blood chemical tests, anthropometrical measures, determination of body composition by bioelectrical impedance, spirometry, and indirect calorimetry. RESULTS: Antibiotic therapy led to a significant improvement in biochemical, spirometric variables and in estimated calorimetry measurements expressed in relation to fat-free mass. These findings suggest that infective exacerbations are among the causes of increased resting energy expenditure in young patients with cystic fibrosis. CONCLUSIONS: Indirect calorimetry may prove useful in the diagnosis of infective exacerbations and in monitoring the effect of antibiotic therapy in patients with cystic fibrosis.

A new mathematical formula for predicting long bone length in early pregnancy.

OBJECTIVE: To propose new mathematical formulae to estimate fetal long bone biometry in early pregnancy and to establish their efficacy in comparison to previously constructed mathematical formulae. METHODS: A study population of 1960 singleton euploid fetuses was referred for transvaginal ultrasound examinations between 71 and 112 days of gestation prior to genetic amniocentesis. To determine the relationship between the biparietal diameter and long bone length, a sample group of 400 randomly chosen normal fetuses was evaluated. Regression equations were derived, then tested in the remaining 1560 control fetuses and compared with previously reported mathematical formulae by other authors. Mean absolute error, mean absolute percentage error and mean systematic error with their standard deviations were calculated. RESULTS: The relationships between femur or humerus length vs. biparietal diameter (BPD) and gestational age (GA) were, respectively: expected femur length = -16.92108 + 0.4569402 x BPD + 0.171617 x GA (P < 0.001) and expected humerus length = -16.28531 + 0.4283019 x BPD + 0.1696017 x GA (P < 0.001). The confidence intervals of the predicted values for different values of biparietal diameter and gestational age and confidence intervals for the regression coefficients, such as the distribution of the residuals, are given. All previous formulae obtained by transabdominal ultrasound demonstrated an overestimation of expected long bones measurements; this was reduced using different formulae obtained in early pregnancy. Using our mathematical formulae, the mean absolute percentage error and the mean systematic error in estimating femur and humerus length were very low (11.15% and -2.02%; 10.59% and -1.74%, respectively). CONCLUSIONS: The new ultrasonographic morphometric models derived from transvaginal measurements in early pregnancy show a good reliability in estimating fetal long bone length.

Endovaginal sonographic diagnosis of the fetal urinary tract anomalies in early pregnancy.

Transvaginal sonography has enhanced the ability to follow fetal development and detect pathologies in early gestation. Examination of the fetal urinary tract is an integral part of routine sonographic examinations in the second trimester of pregnancy and one of the major benefits of prenatal sonography is to allow early diagnosis of relatively common urinary tract malformations. Detailed evaluation of the fetal urinary tract and identification of anomalies were considered to be difficult before the 18th week of gestation prior to the use of transvaginal sonography. Using the transvaginal route, a detailed evaluation of the kidneys is possible around 12 weeks and structural anomalies of the urinary tract are being detected at an ever-increasing rate. Transvaginal sonography, owing to its proximity to the maternal pelvic organs, allows an earlier determination of the normal fetal urinary system and more accurate diagnosis and identification of fetal urinary anomalies as compared with transabdominal ultrasound.

[Estimate of fetal long bone length in early pregnancy: comparison between mathematical formulae]. / Stima della lunghezza delle ossa lunghe fetali in epoca precoce di gravidanza: confronto tra formule matematiche.

BACKGROUND: The aim of this study was to determine the efficacy of different mathematical formulae described in the literature and to propose new mathematical formulae to estimate fetal long bones biometry in early pregnancy. METHODS: In 1481 singleton euploid fetuses a transvaginal ultrasound examination was performed between 9 and 16 week's gestation. To determine the relationship between the biparietal diameter and long bone lengths, a sample group of 100 randomly chosen normal fetuses was evaluated by regression equations. The equations derived were then tested in the remaining 1381 control fetuses and the mean absolute percentage error and the mean systematic error with their standard deviations were compared with previously reported mathematical formulae by other authors. RESULTS: All previous formulae described in literature when applied to our population revealed an overestimation of expected long bones measurements. Using our mathematical formulae, the mean absolute percentage error and the mean systematic error were 11.5% and 1% in estimating femur and 10.9% and 0.8% in estimating humerus length, respectively. CONCLUSIONS: These newly derived ultrasound morphometric formulae could be proposed as reliable models in estimating fetal long bone lengths in early pregnancy.

Comparison of two enteric coated microsphere preparations in the treatment of pancreatic exocrine insufficiency caused by cystic fibrosis.

BACKGROUND: Pancreatic exocrine insufficiency is a common condition in patients with cystic fibrosis. Large amounts of pancreatic enzyme supplements are required to reduce malabsorption but patient compliance is not always optimal. AIMS: To compare patients' preference and the efficacy of two enteric coated microsphere preparations in patients with cystic fibrosis. PATIENTS: Patients with pancreatic exocrine insufficiency due to cystic fibrosis. METHODS: Patients were assigned to the crossover treatment with Creon or Pancrease for 1 week and then to the alternative treatment. Patients had to follow a fixed diet (at least 2 g fat/kg) and had to assume 1000 units lipase/g fat. The evaluation parameters were: patients' preference, acceptance of therapy, stool fat excretion, stool weight, gastrointestinal symptoms, and tolerance. RESULTS AND CONCLUSIONS: Of the 33/60 patients who expressed a preference for one of the two treatments, 30 preferred Creon while only 3 patients preferred Pancrease (p<0.001). No difference between the two treatments was observed regarding stool characteristics, gastrointestinal symptoms and tolerance. The mean number of capsules taken daily was reduced by 35% with Creon. The results of this study showed a preference in favour of Creon probably due to the reduction of daily capsule intake of 35%, supporting digestion as well as Pancrease.

Acceptability of early transvaginal or abdominal sonography in the first half of pregnancy.

OBJECTIVE: To evaluate the acceptability of early transvaginal sonography by pregnant patients. METHODS: A questionnaire was completed by 246 patients and the resulting data were analysed. RESULTS: The incidence of discomfort was higher for the transabdominal than for the transvaginal route. Moreover, the transvaginal approach in early pregnancy, when compared with other transvaginal sonographic examinations was described as more satisfactory in 95% of cases. CONCLUSIONS: Transvaginal sonography in early pregnancy is better tolerated than transabdominal sonography.