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.

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.

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).

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.

GRB 130427A: a nearby ordinary monster.

Long-duration gamma-ray bursts (GRBs) are an extremely rare outcome of the collapse of massive stars and are typically found in the distant universe. Because of its intrinsic luminosity (L ~ 3 × 10(53) ergs per second) and its relative proximity (z = 0.34), GRB 130427A reached the highest fluence observed in the γ-ray band. Here, we present a comprehensive multiwavelength view of GRB 130427A with Swift, the 2-meter Liverpool and Faulkes telescopes, and by other ground-based facilities, highlighting the evolution of the burst emission from the prompt to the afterglow phase. The properties of GRB 130427A are similar to those of the most luminous, high-redshift GRBs, suggesting that a common central engine is responsible for producing GRBs in both the contemporary and the early universe and over the full range of GRB isotropic energies.

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.

Atypical Epstein-Barr-Virus infection in a 5-year-old girl.

Primary Epstein-Barr virus (EBV) infection is often asymptomatic before five years of age, whereas it is more likely to be symptomatic in older children, adolescents and young adults. The classic triad of symptoms including fever, pharyngitis and lymphadenopathy is well known, but the spectrum of clinical manifestations associated with EBV infection is large and continues to expand, including increasing atypical presentations. This article presents the case of a five-year-old female in which only a protracted and severe itch, resistant to antihistamines, caught the attention of the girl's parents, thus allowing the diagnosis of EBV. Furthermore, EBV related splenomegaly and mild hepatitis as well as thrombocytopenia had an atypical prolonged course.

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.

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.

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.

Recombinant interferon alfa 2a in hepatic hemangiomatosis with congestive heart failure: a case report.

A 45-day-old patient was admitted with dyspnea, hepatomegaly, tachycardia, holosystolic murmur in the precordial region, and continuous murmur at the right hypochondrium. Four cutaneous angiomas were noted. Instrumental examinations revealed congestive heart failure and multiple focal lesions in the liver with typical features of hemangiomas. The therapy with subcutaneous interferon-alfa-2a (IFN-alpha) was administered for 12 months with progressive regression of cutaneous hemangiomas, liver lesions, and cardiological alterations. IFN-alpha therapy was effective without any significant adverse effects.

[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.

A long-term follow-up of autoaugmentation in myelodysplastic children.

OBJECTIVE: To evaluate the long-term results of patients who underwent bladder autoaugmentation (BA) in whom BA was used to treat a neuropathic bladder secondary to myelomeningocele, and who presented with a high-pressure/poorly compliant bladder. PATIENTS AND METHODS: Eleven patients (eight girls and three boys, mean age 12.8 years, mean follow-up 6.6 years) were selected who had undergone BA between June 1991 and June 1994. At surgery, the patients had a poorly compliant bladder with a mean leak point volume (LPV) of 94 mL and a mean leak point pressure (LPP) of 58 cmH2O. None of the patients had vesico-ureteric reflux (VUR) at BA; five with grade III or IV VUR had undergone endoscopic correction in a day-surgery procedure using a suburethral collagen injection 1-3 weeks before BA. The patients were evaluated using clinical, urodynamic, radiological and endoscopic assessments. The LPV, LPP and safe bladder capacity (SBC, the cystometric volume at an intravesical pressure of 40 cmH2O) were recorded. RESULTS: At 1 year after surgery the mean LPV was 297 mL; none of the patients had VUR. The most recent mean LPV was 198 mL and the SBC 167 mL. The mean LPP remained stable at 60 cmH2O. At the last follow-up four patients had recurrent uni- or bilateral grade III-V VUR. At endoscopy the 'augmented' bladder portion had a smooth surface, compared with the grossly trabeculated lower half. From this finding all patients on clean intermittent catheterization were treated with oral oxybutynin. Some patients reported slightly less abdominal pain at maximum bladder volume; four needed pads to treat intermittent incontinence. On voiding cysto-urethrography, one patient had an hourglass-shaped bladder. Five patients recently underwent ileocystoplasty because of recurrent urinary tract infection, high-grade VUR and incontinence. CONCLUSION: These results do not justify the routine use of BA in hypertonic/poorly compliant bladders secondary to myelomeningocele. The mean follow-up of 6.6 years showed that this procedure failed in seven of 11 patients. Further studies might be able to identify subgroups in which this approach may be more appropriate.

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.

Electromyographic and manometric anorectal evaluation in children affected by neuropathic bladder secondary to myelomeningocele.

BACKGROUND: Fecal incontinence, with or without persistent constipation is often underestimated in children affected by spina bifida. Medullar lesions to the L-S metameres result in a slowing of rectal and/or rectal-sigmoid motility, loss of anal or rectal sensation, deranged external anal sphincter function, altered motility of the anal levator muscles, and loss of motor coordination of the internal sphincter. We conducted an electromyographic and electromanometric evaluation of the anorectal tract in a group of children affected by myelomeningocele (MMC) in an attempt to evaluate the degree of functional damage and to provide appropriate treatment. METHODS: Anorectal manometry was conducted in 83 children affected by MMC (2-16 yrs, mean age: 8.4 yrs); surface electromyography was also performed in 37 of these children. We thus evaluated overall sphincter pressure, the inhibitory anal reflex, the rectal sphincteric reflex and rectal motility during stimulation and at rest. Recording perfusion catheters (0.1 ml/sec) were placed at rectal and anal level; rectal stimulation was conducted with an endorectal balloon. RESULTS: In all patients there was a reduction in overall sphincter pressure (15-25 mmHg; n.v. 45+/-25 mmHg) and the functional length of the anal canal (1-1.8 cm) compared with age matched controls. The inhibitory anal reflex was normal in all patients, although its amplitude, duration and sensitivity were not constant. Similar findings were obtained for the rectal-sphincteric reflex. The rectal sigmoid motility results were difficult to interpret: sudden, fast and high pressure waves of peristaltic progression were followed by prolonged pauses. No correlation was found between urodynamic and anorectal manometric data. Treatment consisted in daily emptying of the rectum so as to avoid fecal retention. Fifteen patients, who presented prolapse and sphincteric hypotonia (

Functional evaluation of tubularized-incised plate repair of midshaft-proximal hypospadias using uroflowmetry.

OBJECTIVE: To determine objectively, using uroflowmetry, the functional results of the tubularized-incised plate urethroplasty to repair midshaft-proximal hypospadias. PATIENTS AND METHODS: Twenty-one patients (mean age 4 years, mean follow-up 1.8 years) were selected from those undergoing surgery between January 1996 and January 1998 at our institution. All patients had midshaft-proximal hypospadias and were treated using the Snodgrass technique. Patients were included if they were able to void volitionally and had no fistula. The flow pattern, maximum (Qmax) and mean flow rate (Qave) were measured; the results were expressed as percentiles and compared with published values from normal children. The Qmax and Qave were considered normal if > 25th percentile, as equivocally obstructed when in the 5-25th percentile and obstructed if < 5th percentile. RESULTS: Fourteen patients were considered normal, four as equivocally obstructed and three as obstructed. Of the second group, one patient had a urethral diverticulum at the native meatus (confirmed by voiding cysto-urethrography) and the remaining three patients had meatal stenosis that responded to dilatation, with normal flow in two and improvement in the other. Of the obstructed group, one patient responded to dilatation and two underwent meatoplasty. CONCLUSION: The tubularized-incised plate repair provides satisfactory functional results for midshaft-proximal hypospadias; uroflowmetry is an important noninvasive tool to evaluate this technique. A long-term follow-up is needed to confirm these results.

In vitro evolution of the human immunodeficiency virus type 1 gag-protease region and maintenance of reverse transcriptase resistance following prolonged drug exposure.

We studied the human immunodeficiency virus type 1 phenotypic and genotypic profiles of a dual drug-resistant isolate (isolate 14aPost-DR) selected for zidovudine (ZDV) and lamivudine (3TC) resistance and then cultured in the presence of 3TC and a protease inhibitor: indinavir (IDV), ritonavir, or KNI-272. The IDV-treated virus was highly resistant to 3TC, ZDV, and IDV and accumulated protease mutations at positions M46I and V82F. A change from alanine to valine was observed in 4 of 10 clones in the P2 position of the p7-p1 Gag-protease cleavage site, linked to position M46I in the dominant viral quasispecies. Previous 3TC resistance did not impair the development of additional mutations in the protease and Gag-protease cleavage regions.

[Mouth mucosa free-flap grafts in repeat operations of hypospadias]. / Innesti di lembi liberi di mucosa buccale nei reinterventi di ipospadia.

BACKGROUND AND AIMS: Buccal mucosal grafts are widely used in the treatment of primary hypospadias and urethral stenosis owing to their elasticity, optimal attachment, possibility of generous harvesting and easy preparation. The aim of this study was to check whether buccal mucosal flaps are also valuable in redo surgery for hypospadias complicated by large breaks in the urethra and with scarce residual genital tissue. METHODS: Fourteen patients aged between 3 and 11 years old (mean age 6.6) were selected and operated between December 1993 and June 1999. The patients presented extensive fistulous tracts, roughly ellipsoidal in shape and with a maximum diameter of between 7 and 42 mm (mean length 18 mm). The original technique was: Duplay (7 patients); Onlay buccal graft (1 patient); Snodgrass (1 patient); Tubulised preputial flap (2 patients); Onlay preputial graft (2 patients); Tubulised vesical mucosal flap (1 patient). The mucosal flap, taken from the lower lip, was used to cover the gap as an onlay patch and recovered with residual genital skin with the interposition, where possible, of a de-epithelised flap. RESULTS: An optimal cosmetic and functional result was achieved in 10/14 cases with flowmetry > 25 percentile according to Toguri nomograms. Three patients presented fistulas: one punctiform fistula resolved spontaneously. The other two cases resolved after corrective surgery. One patient showed meatal regression with slight stenosis that was resolved with MAGPI. CONCLUSIONS: These results appear to be encouraging. Buccal mucosal graft may represent a valid alternative also in the treatment of secondary hypospadia with large breaks in the urethra. No complication was reported in the harvesting area, even if this was carried out at a second stage in the labial area.