Observation of inverse Compton emission from a long γ-ray burst.

Long-duration γ-ray bursts (GRBs) originate from ultra-relativistic jets launched from the collapsing cores of dying massive stars. They are characterized by an initial phase of bright and highly variable radiation in the kiloelectronvolt-to-megaelectronvolt band, which is probably produced within the jet and lasts from milliseconds to minutes, known as the prompt emission1,2. Subsequently, the interaction of the jet with the surrounding medium generates shock waves that are responsible for the afterglow emission, which lasts from days to months and occurs over a broad energy range from the radio to the gigaelectronvolt bands1-6. The afterglow emission is generally well explained as synchrotron radiation emitted by electrons accelerated by the external shock7-9. Recently, intense long-lasting emission between 0.2 and 1 teraelectronvolts was observed from GRB 190114C10,11. Here we report multi-frequency observations of GRB 190114C, and study the evolution in time of the GRB emission across 17 orders of magnitude in energy, from 5 × 10-6 to 1012 electronvolts. We find that the broadband spectral energy distribution is double-peaked, with the teraelectronvolt emission constituting a distinct spectral component with power comparable to the synchrotron component. This component is associated with the afterglow and is satisfactorily explained by inverse Compton up-scattering of synchrotron photons by high-energy electrons. We find that the conditions required to account for the observed teraelectronvolt component are typical for GRBs, supporting the possibility that inverse Compton emission is commonly produced in GRBs.

Malignant ovarian germ cell tumors in pediatric patients: The AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica) study.

OBJECTIVE: Malignant ovarian germ cell tumors (MOGCT) carry an excellent prognosis, and the treatment aims to achieve results with the least possible treatment-related morbidity. The aim of this study was to assess the outcomes of pediatric patients with MOGCT. METHODS: Patients were treated according to their stage: surgery and surveillance for stage I; a modified bleomycin-etoposide-cisplatin (BEP) regimen for stages II (three cycles), III, and IV (three cycles) with surgery on residual disease. RESULTS: Seventy-seven patients were enrolled (median age 11.8 years), 26 with dysgerminoma (Dysg), 13 with immature teratoma and elevated serum alpha-fetoprotein levels (IT + AFP), and 38 with nondysgeminoma (Non-Dysg) staged as follows: 27 stage I, 13 stage II, 32 stage III, 5 stage IV. Among evaluable patients in stage I (5-year event-free survival [EFS] 72.1% [95% CI: 56.4-92.1%]; 5-year overall survival [OS] 100%), seven relapsed (three patients with Dysg and four patients with Non-Dysg) and were rescued with chemotherapy (plus surgery in three patients). Among the evaluable patients with stages II-IV, 48 (98%) achieved complete remission after chemotherapy ± surgery, one (IT + AFP, stage IV) had progressive disease. In the whole series (median follow-up 80 months), the 5-year OS and EFS were 98.5% (95% CI: 95.6-100%) and 84.5% (95% CI: 76.5-93.5%). CONCLUSIONS: We confirm the excellent outcome for MOGCT. Robust data are lacking on surgical staging, surveillance for Non-Dysg with stage I, the management of IT + AFP, and the most appropriate BEP regimen. As pediatric oncologists, we support the role of surveillance after proper surgical staging providing cases are managed by experts at specialized pediatric centers.

The unusual γ-ray burst GRB 101225A from a helium star/neutron star merger at redshift 0.33.

Long γ-ray bursts (GRBs) are the most dramatic examples of massive stellar deaths, often associated with supernovae. They release ultra-relativistic jets, which produce non-thermal emission through synchrotron radiation as they interact with the surrounding medium. Here we report observations of the unusual GRB 101225A. Its γ-ray emission was exceptionally long-lived and was followed by a bright X-ray transient with a hot thermal component and an unusual optical counterpart. During the first 10 days, the optical emission evolved as an expanding, cooling black body, after which an additional component, consistent with a faint supernova, emerged. We estimate its redshift to be z = 0.33 by fitting the spectral-energy distribution and light curve of the optical emission with a GRB-supernova template. Deep optical observations may have revealed a faint, unresolved host galaxy. Our proposed progenitor is a merger of a helium star with a neutron star that underwent a common envelope phase, expelling its hydrogen envelope. The resulting explosion created a GRB-like jet which became thermalized by interacting with the dense, previously ejected material, thus creating the observed black body, until finally the emission from the supernova dominated. An alternative explanation is a minor body falling onto a neutron star in the Galaxy.

GRB 090423 at a redshift of z approximately 8.1.

Gamma-ray bursts (GRBs) are produced by rare types of massive stellar explosion. Their rapidly fading afterglows are often bright enough at optical wavelengths that they are detectable at cosmological distances. Hitherto, the highest known redshift for a GRB was z = 6.7 (ref. 1), for GRB 080913, and for a galaxy was z = 6.96 (ref. 2). Here we report observations of GRB 090423 and the near-infrared spectroscopic measurement of its redshift, z = 8.1(-0.3)(+0.1). This burst happened when the Universe was only about 4 per cent of its current age. Its properties are similar to those of GRBs observed at low/intermediate redshifts, suggesting that the mechanisms and progenitors that gave rise to this burst about 600,000,000 years after the Big Bang are not markedly different from those producing GRBs about 10,000,000,000 years later.

An extremely luminous X-ray outburst at the birth of a supernova.

Massive stars end their short lives in spectacular explosions--supernovae--that synthesize new elements and drive galaxy evolution. Historically, supernovae were discovered mainly through their 'delayed' optical light (some days after the burst of neutrinos that marks the actual event), preventing observations in the first moments following the explosion. As a result, the progenitors of some supernovae and the events leading up to their violent demise remain intensely debated. Here we report the serendipitous discovery of a supernova at the time of the explosion, marked by an extremely luminous X-ray outburst. We attribute the outburst to the 'break-out' of the supernova shock wave from the progenitor star, and show that the inferred rate of such events agrees with that of all core-collapse supernovae. We predict that future wide-field X-ray surveys will catch each year hundreds of supernovae in the act of exploding.

A short gamma-ray burst apparently associated with an elliptical galaxy at redshift z = 0.225.

Gamma-ray bursts (GRBs) come in two classes: long (> 2 s), soft-spectrum bursts and short, hard events. Most progress has been made on understanding the long GRBs, which are typically observed at high redshift (z approximately 1) and found in subluminous star-forming host galaxies. They are likely to be produced in core-collapse explosions of massive stars. In contrast, no short GRB had been accurately (< 10'') and rapidly (minutes) located. Here we report the detection of the X-ray afterglow from--and the localization of--the short burst GRB 050509B. Its position on the sky is near a luminous, non-star-forming elliptical galaxy at a redshift of 0.225, which is the location one would expect if the origin of this GRB is through the merger of neutron-star or black-hole binaries. The X-ray afterglow was weak and faded below the detection limit within a few hours; no optical afterglow was detected to stringent limits, explaining the past difficulty in localizing short GRBs.

Propofol-based palliative sedation in terminally ill children with solid tumors: A case series.

RATIONALE: The palliative sedation therapy is defined as the intentional reduction of the alert state, using pharmacological tools. Propofol is a short-acting general anesthetic agent, widely used for induction and maintenance of general anesthesia and rarely employed in palliative care. PATIENT CONCERNS AND DIAGNOSES: This case series describes 5 pediatric oncology inpatients affected by relapsed/refractory solid tumors received palliative sedation using propofol alone or in combination with opioids and benzodiazepines. INTERVENTIONS AND OUTCOMES: Five terminally ill children affected by solid tumors received propofol-based palliative sedation. All patients were previously treated with opioids and some of them reduced the consumption of these drugs after propofol starting. In all cases the progressive increase of the level of sedation until the death has been the only effective measure of control of refractory symptoms related todisease progression and psychological suffering. LESSONS: We evaluated the quality of propofol-based palliative sedation in a series of pediatric oncology patients with solid tumors at the end of their life. We concluded that propofol represents an effective and tolerable adjuvant drug for the management of intractable suffering and a practicable strategy for palliative sedation in pediatric oncology patients at the end of their life.

Expression of transglutaminase 2 does not differentiate focal myositis from generalized inflammatory myopathies.

OBJECTIVES: Idiopathic inflammatory myopathies (IIM), including dermatomyositis (DM), polymyositis (PM), sporadic inclusion-body myositis (s-IBM) and focal myositis (FM) are a heterogeneous group of autoimmune disorders of skeletal muscle. An increased transglutaminase 2 (TG2) expression has been found in DM, PM and s-IBM. The aim of our study was to investigate TG2 expression in FM in comparison with other IIM. MATERIALS AND METHODS: We re-examined tissue material we have gathered in the course of our previous studies on IIM, investigating muscle expression of TG2 in patients with FM in comparison with DM, PM and s-IBM using immunocytochemistry and real-time RT-PCR. RESULTS: Immunocytochemistry revealed an increased TG2 signal in endomysial vessels, in atrophic and degenerating/regenerating muscle fibres in PM, DM, s-IBM and FM; in s-IBM, some vacuoles were immunostained too. Real-time RT-PCR study confirmed a significantly increased expression of TG2 in all IIM muscles examined. CONCLUSIONS: Our study demonstrates the presence of TG2 in FM muscles. The study suggests that TG2 expression does not represent a distinctive marker to differentiate FM from generalized IIM. TG2 over-expression in inflamed skeletal muscle does not seem have a pathogenetic role in such a disease, but it could represent a way to contain the inflammatory process.

Micellar electrokinetic chromatography with laser induced fluorescence detection shows increase of putrescine in erythrocytes of Parkinson's disease patients.

A highly sensitive method was developed to measure putrescine by micellar electrokinetic chromatography with laser induced fluorescence detection with excellent linearity in the 1 nM to 3 µM range. The technique was tested on a drop of blood from Parkinson's disease patients obtained by finger prick. The results showed a statistically significant increase of putrescine in the erythrocytes compared to controls and a non-significant increase in plasma. This high level of putrescine does not constitute by itself proof that putrescine and polyamines are directly related to Parkinson's disease. However, the present results and several others addressed in the discussion suggest that these compounds might be causally involved in the pathophysiology of Parkinson's disease. In addition, the analytical method reported here may help to find new biomarkers for many diseases including Parkinson's disease.

Swift and NuSTAR observations of GW170817: Detection of a blue kilonova.

With the first direct detection of merging black holes in 2015, the era of gravitational wave (GW) astrophysics began. A complete picture of compact object mergers, however, requires the detection of an electromagnetic (EM) counterpart. We report ultraviolet (UV) and x-ray observations by Swift and the Nuclear Spectroscopic Telescope Array of the EM counterpart of the binary neutron star merger GW170817. The bright, rapidly fading UV emission indicates a high mass (≈0.03 solar masses) wind-driven outflow with moderate electron fraction (Ye ≈ 0.27). Combined with the x-ray limits, we favor an observer viewing angle of ≈30° away from the orbital rotation axis, which avoids both obscuration from the heaviest elements in the orbital plane and a direct view of any ultrarelativistic, highly collimated ejecta (a γ-ray burst afterglow).

Viral load, viral phenotype modification, zidovudine susceptibility and reverse transcriptase mutations during the first 6 months of zidovudine monotherapy in HIV-1-infected people.

We studied 14 zidovudine-naive, HIV-1-infected patients attending an infectious diseases clinic in Milan during zidovudine therapy for 6 months. We monitored CD4 cell counts, immune complex-dissociated p24 antigen, viral phenotype and viral load in plasma. The virus infecting a subset of patients was examined for zidovudine susceptibility and zidovudine resistance-associated mutations. A significant correlation was established between the increase in the CD4 cell count and the decrease in viral load (Spearman's coefficients < -0.5). Patients who were p24 antigen positive had a higher viral load (P < 0.005 at baseline and after 6 months of therapy). Patients with non-syncytium-inducing (NSI) virus had higher CD4 cell counts over time than those with syncytium-inducing (SI) virus. We also examined the viral load in relation to viral phenotype. The median viral load in patients with NSI virus was higher than in SI controls at baseline, but not after 3 and 6 months of therapy. Sequential isolates of HIV-1 were obtained from nine patients and tested for resistance to zidovudine by monitoring the drug susceptibility and the reverse transcriptase-encoding sequence. Amino acid changes at codons 70 and 215 were present in some but not all isolates with zidovudine-resistant phenotype in vitro. It was possible to perform a correlation between zidovudine susceptibility and zidovudine-associated pol gene mutations only at the 6-month time point (Spearman's coefficient = 0.076). SI phenotype was associated with the development of a decreased zidovudine susceptibility. A correlation between zidovudine-associated pol gene mutations and SI phenotype was detected at the 6-month time point.

Loss of lamivudine resistance in a zidovudine and lamivudine dual-resistant HIV-1 isolate after discontinuation of in vitro lamivudine drug pressure.

We examined the in vitro phenotypic and genotypic profiles of an extensively passaged human immunodeficiency virus type 1 clinical isolate which has been selected for lamivudine resistance, with an M184V mutation in a zidovudine-resistant genetic background, and then cultured with zidovudine alone. Our passaging strategy led to a decrease in lamivudine IC50 values, which were comparable to those prior to lamivudine exposure, and the genotypic restoration of the wild-type sequence at codon 184 of reverse transcriptase.

Loss of antiviral effect owing to zidovudine and lamivudine double resistance in HIV-1-infected patients in an ongoing open-label trial.

In order to compare the resistance pattern to zidovudine plus lamivudine in zidovudine-experienced patients, we studied three HIV-1-infected patients enrolled in NUCB3004, an open-label trial. Over a 24-week follow-up, the patients were studied for drug sensitivity, reverse transcriptase genotype, viral load (HIV-1 RNA level) and viral phenotype (syncytium inducing (SI) or non-syncytium inducing). Virus isolates derived from peripheral blood mononuclear cells (PBMCs) were tested for changes in drug susceptibility. Proviral DNA in the patients' PBMCs and RNA from plasma and culture supernatant were subjected to amplification and sequencing. All three HIV-1 strains showed a decreased susceptibility to either zidovudine or lamivudine after 24 weeks of therapy. The pattern of DNA genotypic resistance to lamivudine in patient A showed a mutation at codon 184 of the reverse transcriptase-encoding gene (methionine to valine). No HIV-1 strains with lamivudine-related mutations in proviral DNA were found among the isolates obtained from patients B and C. In these two patients, the mutation at codon 184 of the reverse transcriptase-encoding gene appeared in RNA, both in plasma and in culture supernatant. Viral phenotyping revealed the maintenance of the SI phenotype at week 24. Two out of the three patients experienced a reduction in HIV-1 RNA levels after 24 weeks of therapy, and in two out of three there was a rebound in viral load at week 28 together with the onset of the codon 184 mutation in RNA. The degree of phenotypic resistance to both zidovudine and lamivudine correlated with the amino acid changes in RNA and the rapid increase in viral load.

HIV-1 reverse transcriptase codon 215 mutation and clinical outcome in children treated with zidovudine.

OBJECTIVE: In HIV-infected adults prolonged monotherapy with zidovudine may be associated with the appearance of HIV strains with decreased zidovudine sensitivity, owing to specific mutations in the reverse transcriptase (RT) gene, and this has been suggested to be a reason for reduced zidovudine efficacy. This study was undertaken to determine the appearance of mutation at codon 215 of the RT gene in proviral DNA from PBMCs in HIV-infected children. DESIGN: A prospective, open study. SETTING: A University Pediatric Department. PATIENTS AND METHODS: Nineteen HIV-infected symptomatic children were treated with zidovudine for a median of 24 months. Clinical and laboratory controls for HIV infection status were performed monthly. Mutant proviral sequences were evaluated at the start of therapy, every 3 months during the first 6 months of therapy, and every 6 months thereafter. Clinical outcome was defined as stable or deteriorating. RESULTS: No child had proviral sequences mutant at codon 215 before starting zidovudine. Ten of 13 children who had received zidovudine for more than 6 months developed mutant proviral sequences. All the children (10 of 10) with mutant proviral sequences had a deteriorating clinical condition, compared to none of those (0 of 9) without mutation at codon 215. CONCLUSION: The appearance of HIV-1 codon 215 mutation seems to be strongly associated with zidovudine therapy and with clinical progression of HIV disease in children.

HIV type 1 phenotype correlates with the stage of infection in vertically infected children.

A cohort of 39 vertically infected children (class N, A, B, and C of the CDC HIV classification for pediatric infection) was studied by virus isolation and non-syncytium inducing (NSI)/syncytium inducing (SI) HIV-1 phenotype evaluation. The HIV-1 isolates were recovered from PBMCs and the MT-2 cell line was used to perform the syncytium assay. HIV-1 could be isolated in 34 of 39 (87%) infected children, regardless of the clinical and immunological stage of the disease. Class N and A subjects harbored exclusively NSI strains, whereas the SI phenotype was detected in two of eight class B and five of nine class C patients. All of the SI variants were observed in severely CD4-depleted children (class 3 patients). The capability of pediatric HIV-1 isolates to induce a cytopathic effect is associated with the clinical status and the degree of CD4 depletion. These data suggest that the biological properties of HIV-1 isolates in children do not differ from those observed in adults, and that viral phenotype strictly correlates with disease progression in vertically infected children.

Comparable biological and molecular determinants in HIV type 1-infected long-term nonprogressors and recently infected individuals.

Human immunodeficiency virus type 1 (HIV-1) isolability, rate of replication, phenotype, plasma viremia, and specific intracellular transcripts were cross-sectionally analyzed in 61 HIV-1-seropositive individuals to evaluate the correlations between the virological and molecular correlates of protection and progression in different clinical subsets: recently infected subjects (RIs), long-term nonprogressors (LTNPs), late progressors (LPs), and typical progressors (TPs). Comparison of the major virological and molecular features of HIV-1 infection has defined distinct profiles for different subsets of patients. LTNPs or RIs, as well as LPs or TPs, exhibited similar titers of coculture p24 antigen; the differences between the former and the latter were statistically significant at all the time points tested (p = 0.0001; 0.0003 and 0.0001). Whereas LTNPs and RIs revealed comparable low levels of indexes of viral replication, LPs and TPs showed higher genome and mRNA copy numbers (p = 0.0004 and p = 0.0008, respectively). We demonstrated close biological and molecular similarities between RIs and LTNPs on the one hand, and LPs and TPs on the other. In LTNPs both viral biological properties and viral load are important determinants of the course of the disease.

MAGPI procedure in meatal regression after hypospadias repair.

OBJECTIVE: To evaluate the efficacy of MAGPI's procedure in children who had a meatal regression after hypospadias repair. PATIENTS AND METHODS: Twenty-one children affected by post-hypospadias repair meatal regression underwent a modified MAGPI repair between January 1992 and January 1999: the patients, aged between 3 and 12 years (mean 5.9), had previously undergone hypospadias repair according to the techniques of Duplay (11 patients), Mathieu (2 patients), Snodgrass (5 patients) or the onlay buccal mucosa graft (3 patients). The outcome of the procedure was evaluated in terms of urinary stream and cosmetic appearance. RESULTS: The results were good in 18 patients, fair in 2, unchanged in 1. CONCLUSIONS: MAGPI's repair has proven to be very effective as a secondary procedure in meatal regression after hypospadias correction, with minimal morbidity and a highly successful outcome in terms of satisfactory functionality and cosmetic appearance, and the recovery of gaps as large as 9 mm.

[Purified human IgG administration, after chemotherapy, to patients with colorectal carcinoma]. / La somministrazione, dopo chemioterapia, di IgG umane purificate in pazienti affetti da carcinoma del colon-retto.

The authors, in the present study try to test the prophylactic effect of human IgG on surgical patients affected by colorectal cancer and undergoing chemotherapy in order to prevent microbial infections, supporting immunological host defences.

[Clinical comments on a case of retroperitoneal lipoma]. / Considerazioni cliniche su di un caso di lipoma retroperitoneale.

The authors show a case of retroperitoneal lipoma, histologically ascertained; they state its origin and the clinical features, and analyse the different diagnostical methods, particularly dwelling upon urography, TC and selective arteriography. They, at last, point out such pathology, although benign, is burdened by a high risk of relapses and by the possibility to turn into malignant. As a conclusion, they assert the importance of the radicalness of the intervention, joined to bioptic drawings in different parts of the tumor extirpated, with the purpose to identify, as precociously as possible, an eventual malignant degeneration of the same lipoma.

[Peripheral blood stem cell collection in pediatric malignancies: comparison between three mobilizing regimens]. / La raccolta di cellule staminali periferiche nei tumori pediatrici: confronto fra tre sistemi di mobilizzazione.

PURPOSE: The optimal method for PBSC (peripheral blood stem cells) mobilization in pediatric patients is still unknown. The present study was conducted to evaluate the safety of apheresis procedures and to compare the efficacy of three methods of PBSC mobilization. PATIENTS AND METHODS: Our study was performed on 28 pediatric patients (in three groups) with solid tumors at onset or on relapse. In two groups we tried to mobilize PBSC administering CHT (based on Carboplatin with Etoposide in the first group and Cyclophosphamide in the second group) followed by granulocyte colony stimulating factor (G-CSF); in the third group the mobilization regimen was based on G-CSF alone. RESULTS: Forty-nine mobilizations have been performed and a median of 6.5 CD34+ cells x 10(6)/Kg were collected, with a median number of one apheresis for each patient. Using Carboplatin with G-CSF and Cyclophosphamide with G-CSF we collected respectively a median value of 6.75 and 7.3 x 10(6) CD34+ cells/kg. The mobilization method based on G-CSF alone showed to be less effective (median of 4.3 CD34+ cells x 10(6)/kg collected). CONCLUSIONS: In our experience the mobilizing regimens based on Carboplatin or Cyclophosphamide associated with G-CSF resulted both effective and better than the one based on G-CSF alone with a scanty number of apheresis procedures.