A very-high-energy component deep in the γ-ray burst afterglow.

Gamma-ray bursts (GRBs) are brief flashes of γ-rays and are considered to be the most energetic explosive phenomena in the Universe1. The emission from GRBs comprises a short (typically tens of seconds) and bright prompt emission, followed by a much longer afterglow phase. During the afterglow phase, the shocked outflow-produced by the interaction between the ejected matter and the circumburst medium-slows down, and a gradual decrease in brightness is observed2. GRBs typically emit most of their energy via γ-rays with energies in the kiloelectronvolt-to-megaelectronvolt range, but a few photons with energies of tens of gigaelectronvolts have been detected by space-based instruments3. However, the origins of such high-energy (above one gigaelectronvolt) photons and the presence of very-high-energy (more than 100 gigaelectronvolts) emission have remained elusive4. Here we report observations of very-high-energy emission in the bright GRB 180720B deep in the GRB afterglow-ten hours after the end of the prompt emission phase, when the X-ray flux had already decayed by four orders of magnitude. Two possible explanations exist for the observed radiation: inverse Compton emission and synchrotron emission of ultrarelativistic electrons. Our observations show that the energy fluxes in the X-ray and γ-ray range and their photon indices remain comparable to each other throughout the afterglow. This discovery places distinct constraints on the GRB environment for both emission mechanisms, with the inverse Compton explanation alleviating the particle energy requirements for the emission observed at late times. The late timing of this detection has consequences for the future observations of GRBs at the highest energies.

Search for γ-Ray Line Signals from Dark Matter Annihilations in the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

Spectral lines are among the most powerful signatures for dark matter (DM) annihilation searches in very-high-energy γ rays. The central region of the Milky Way halo is one of the most promising targets given its large amount of DM and proximity to Earth. We report on a search for a monoenergetic spectral line from self-annihilations of DM particles in the energy range from 300 GeV to 70 TeV using a two-dimensional maximum likelihood method taking advantage of both the spectral and spatial features of the signal versus background. The analysis makes use of Galactic center observations accumulated over ten years (2004-2014) with the H.E.S.S. array of ground-based Cherenkov telescopes. No significant γ-ray excess above the background is found. We derive upper limits on the annihilation cross section ⟨σv⟩ for monoenergetic DM lines at the level of 4×10^{-28} cm^{3} s^{-1} at 1 TeV, assuming an Einasto DM profile for the Milky Way halo. For a DM mass of 1 TeV, they improve over the previous ones by a factor of 6. The present constraints are the strongest obtained so far for DM particles in the mass range 300 GeV-70 TeV. Ground-based γ-ray observations have reached sufficient sensitivity to explore relevant velocity-averaged cross sections for DM annihilation into two γ-ray photons at the level expected from the thermal relic density for TeV DM particles.

Search for Dark Matter Annihilations towards the Inner Galactic Halo from 10 Years of Observations with H.E.S.S.

The inner region of the Milky Way halo harbors a large amount of dark matter (DM). Given its proximity, it is one of the most promising targets to look for DM. We report on a search for the annihilations of DM particles using γ-ray observations towards the inner 300 pc of the Milky Way, with the H.E.S.S. array of ground-based Cherenkov telescopes. The analysis is based on a 2D maximum likelihood method using Galactic Center (GC) data accumulated by H.E.S.S. over the last 10 years (2004-2014), and does not show any significant γ-ray signal above background. Assuming Einasto and Navarro-Frenk-White DM density profiles at the GC, we derive upper limits on the annihilation cross section ⟨σv⟩. These constraints are the strongest obtained so far in the TeV DM mass range and improve upon previous limits by a factor 5. For the Einasto profile, the constraints reach ⟨σv⟩ values of 6×10^{-26} cm^{3} s^{-1} in the W^{+}W^{-} channel for a DM particle mass of 1.5 TeV, and 2×10^{-26} cm^{3} s^{-1} in the τ^{+}τ^{-} channel for a 1 TeV mass. For the first time, ground-based γ-ray observations have reached sufficient sensitivity to probe ⟨σv⟩ values expected from the thermal relic density for TeV DM particles.

Constraints on an annihilation signal from a core of constant dark matter density around the milky way center with H.E.S.S.

An annihilation signal of dark matter is searched for from the central region of the Milky Way. Data acquired in dedicated on-off observations of the Galactic center region with H.E.S.S. are analyzed for this purpose. No significant signal is found in a total of ∼9 h of on-off observations. Upper limits on the velocity averaged cross section, ⟨σv⟩, for the annihilation of dark matter particles with masses in the range of ∼300 GeV to ∼10 TeV are derived. In contrast to previous constraints derived from observations of the Galactic center region, the constraints that are derived here apply also under the assumption of a central core of constant dark matter density around the center of the Galaxy. Values of ⟨σv⟩ that are larger than 3×10^{-24} cm^{3}/s are excluded for dark matter particles with masses between ∼1 and ∼4 TeV at 95% C.L. if the radius of the central dark matter density core does not exceed 500 pc. This is the strongest constraint that is derived on ⟨σv⟩ for annihilating TeV mass dark matter without the assumption of a centrally cusped dark matter density distribution in the search region.

Revealing x-ray and gamma ray temporal and spectral similarities in the GRB 190829A afterglow.

Gamma-ray bursts (GRBs), which are bright flashes of gamma rays from extragalactic sources followed by fading afterglow emission, are associated with stellar core collapse events. We report the detection of very-high-energy (VHE) gamma rays from the afterglow of GRB 190829A, between 4 and 56 hours after the trigger, using the High Energy Stereoscopic System (H.E.S.S.). The low luminosity and redshift of GRB 190829A reduce both internal and external absorption, allowing determination of its intrinsic energy spectrum. Between energies of 0.18 and 3.3 tera-electron volts, this spectrum is described by a power law with photon index of 2.07 ± 0.09, similar to the x-ray spectrum. The x-ray and VHE gamma-ray light curves also show similar decay profiles. These similar characteristics in the x-ray and gamma-ray bands challenge GRB afterglow emission scenarios.

Inorganic pyrophosphate in plasma in normal persons and in patients with hypophosphatasia, osteogenesis imperfecta, and other disorders of bone.

An isotope dilution method, using (32)P-labeled pyrophosphate, has been developed for the measurement of inorganic pyrophosphate (PP(1)) in human plasma. The specificity of the method was better than 90% as assessed by elution patterns during ion-exchange chromatography, by paper chromatography, and by incubation with inorganic pyrophosphatase. The 99% confidence limits for a single estimation of plasma PP(1) was +/-13%. There were no differences in plasma PP(1) between men and women, but the values in young people (0-15 yr) were slightly higher than in older people. The mean concentration (+/-SE) of PP(1) in the plasma of 73 men and women was 3.50 +/-0.11 mumoles/liter (0.217 +/-0.007 mug P/ml) and the normal range (99% limits) was 1.19-5.65 mumoles/liter (0.074-0.350 mug P/ml). It has been suggested that PP(1) may be important in calcium metabolism because PP(1) can prevent the precipitation of calcium phosphates in vitro and in vivo, and can slow the rates at which hydroxyapatite crystals grow and dissolve. Plasma PP(1) was therefore measured in several disorders of bone. Normal values were found in osteogenesis imperfecta, osteopetrosis, "acute" osteoporosis, and primary hyperparathyroidism. Plasma PP(1) was invariably raised in hypophosphatasia. The excess of PP(1) in plasma might be the cause of the defective mineralization in hypophosphatasia and the function of alkaline phosphatase in bone may be to act as a pyrophosphatase at sites of calcium deposition.

[How to recognize POAD? The diagnosis of peripheral occlusive arterial disease in the physician's office]. / Diagnostik der arteriellen Verschlusskrankheit: Mit Stethoskop, Doppler und Laufband der pAVK auf den Fersen.

Peripheral occlusive arterial disease (POAD) encompasses all stenotic and occlusive changes affecting the aorta and arteries supplying the extremities, and in 90% of the cases is due to atherosclerosis. In the majority of patients the lower extremities are involved, andonly every third patient has symptoms. Apart from its significance as an independent disease entity, POAD is also an important coincidence marker, in particular for coronary heart disease. For the diagnostic clarification of POAD, a stepped strategy is recommended, including clinical function testing, such as an exercise treadmill test. Doppler sonography and determination of the Doppler pressure index (ankle-brachial index) make possible a noninvasive accurate staging. Color-coded duplex sonography and imaging procedures provide further information, and are indispensable for establishing the indication for interventional measures.

INSECT PHYLOGENOMICS. Response to Comment on "Phylogenomics resolves the timing and pattern of insect evolution".

Tong et al. comment on the accuracy of the dating analysis presented in our work on the phylogeny of insects and provide a reanalysis of our data. They replace log-normal priors with uniform priors and add a "roachoid" fossil as a calibration point. Although the reanalysis provides an interesting alternative viewpoint, we maintain that our choices were appropriate.

Tomographic imaging of the human thyroid using 124I.

After receiving between 100 and 300 mu Ci of the positron-emitting radioisotope 124I (half-life, 4.2 days), 64 patients with a variety of thyroid disorders were imaged with a high resolution positron camera. A 3-dimensional image of the distribution of radioiodine uptake within the thyroid was obtained from a single 10- to 15-min scan. This image may be viewed as a sequence of 2-mm thick transverse, sagittal, or frontal sections or as a 3-dimensional shaded surface. The functional volume of the thyroid may be estimated by counting the volume elements (voxels) inside the thyroid surface. The precision of the estimate varied from 6-15%, depending on the size and clinical status of the thyroid. The volume estimation procedure was validated with phantoms and with the thyroids of patients who subsequently underwent partial thyroidectomy. This 3-dimensional imaging technique may be useful for diagnosis and management of thyroid diseases.

Calcium absorption from milk in lactase-deficient subjects.

Intestinal calcium absorption from milk containing lactose (+) and from another containing glucose (-) was studied in eight patients with normal lactase (NL) and seven lactase-deficient (LD) subjects to determine if lactase deficiency is implicated in Ca absorption. The results were compared with data obtained from Ca ingestion in a water solution. Ca absorption was measured by a double-isotope technique and the kinetic indices were obtained by a deconvolution method. With (-), Ca absorption was identical in NL and LD subjects and slightly higher than with water solution (15%, NS). With (+), Ca absorption in NL subjects was identical with that from water solution; in LD subjects it increased (23%, p less than 0.02). These data indicate that: Ca is absorbed equally well from milk as from water solution; (+) favors Ca absorption in LD subjects, which suggests that milk ingestion might be encouraged in LD subjects to avoid Ca deficiency; and (-) should be a valuable alternative for lactose-intolerant patients.

A rotating PET scanner using BGO block detectors: design, performance and applications.

Recent advances in fully three-dimensional reconstruction for multi-ring PET scanners have led us to explore the potential of a prototype scanner based on the rotation of two opposing arrays of BGO block detectors. The prototype contains only one-third of the number of detectors in the equivalent full ring scanner, resulting in reduced cost. With a lower energy threshold at 250 keV, the absolute efficiency of the scanner is 0.5% and the scatter fraction is 35% for a 20-cm cylinder. Transaxial and axial spatial resolution is about 6 mm. The maximum noise equivalent count rate estimated for a 15-cm diameter cylinder is 36,000 cps at a concentration of 26 kBq/ml. The minimum scan time for a 18F-fluoro-2-deoxyglucose (FDG) brain study is 55 sec. The camera has been validated for clinical applications using both FDG and 82Rb.

High density avalanche chamber (HIDAC) positron camera.

A prototype positron camera has been constructed consisting of two high density avalanche chamber (HIDAC) detectors operated in coincidence with a resolving time (2 tau) of 40 nsec. The detectors are multiwire chambers, with specially constructed lead converters added to improve the photon detection efficiency at 511 keV. The current HIDAC detectors have a singles efficiency of approximately 12%, a sensitive area of 31 X 31 cm and an intrinsic spatial resolution of less than 2 mm full width at half maximum (FWHM). During data acquisition, the detectors are rotated around the patient in order to collect a complete angular data set. A three-dimensional image of the positron distribution is reconstructed from a single scan by weighted backprojection of the data into a matrix of either 64 X 64 X 64 or 128 X 128 X 16 voxels. The camera point response function is deconvolved by frequency-space filtering. Corrections are made during backprojection both for photon attenuation and for spatial variations in point source sensitivity. The reconstructed image is further corrected for contributions from accidental and scattered coincidences and displayed as a sequence of two-dimensional transverse, sagittal, or coronal sections. In addition, three-dimensional display is available using shaded graphics techniques. The prototype camera is currently undergoing clinical evaluation.

Effects of cardiac surgery on renal function in children.

In order to determine whether cardiac surgery with cardiopulmonary bypass (CPB) affects renal function in children, glomerular filtration rate (GFR and renal plasma flow (RPF) were determined preoperatively and on the second postoperative day by a single-injection, urineless technique in a randomly selected group of 10 children. The GFR was 126.7 +/- 6.8 ml. per minute per 1.73 sq. M. (mean +/- S.E.M.) before the operation and 127.4 +/- 16.2 on the second postoperative day (p = 0.95). The RPF was 541.7 +/- 80.6 ml. per minute per 1.73 sq. M. preoperatively and 536.0 +/- 82.1 on the second postoperative day (p = 0.8 to 0.9). The results in this group of 10 children indicate that renal function is not markedly altered 2 days after cardiac surgery with CPB and deep hypothermia with circulatory arrest. The study also revealed a falsely decreased creatinine clearance. This was due to an increase in postoperative plasma creatinine values, probably related to an increase in plasma noncreatinine chromogens.

Elimination of free radionuclide by a chelating agent improves tumor-to-nontumor ratios following radioimmunotargeting with antibody labeled with 67Ga.

To circumvent radionuclide accumulation in nontarget tissues when employing metallic radionuclides for radioimmunoscintigraphy or radioimmunotherapy, we have investigated the effect of the chelating agent deferroxamine (DFO) on the biodistribution of 67Ga following its administration attached to intact monoclonal antibody MAb35 and its F(ab')2 fragment. Following administration of 67Ga-labeled MAb35, DFO accelerated whole-body elimination of 67Ga and reduced its accumulation in several normal tissues, including liver, spleen and kidney. No reduction in tumor accumulation of 67Ga was observed. Following administration of 67Ga-labeled F(ab')2 fragment, kidney accumulation was higher than with the intact antibody (29% and 4% ID/g, respectively) and blood levels lower (0.69% and 5% ID/g, respectively). Again, no alteration in tumor accumulation of 67Ga was seen following DFO, although liver, kidney and blood levels were reduced and whole-body elimination accelerated.

Use of two virustatica (AZT, PMEA) in the treatment of FIV and of FeLV seropositive cats with clinical symptoms.

In the present study the therapeutic efficacy and the side effects of two antiretroviral compounds used in human acquired immunodeficiency syndrome (AIDS) research, 3'-azido-2',3'-dideoxythymidine (AZT, zidovudine, Retrovir) and 9-(2-phosphonylmethoxyethyl)adenine (PMEA), were investigated in the treatment of cats naturally infected with feline immunodeficiency virus (FIV) and cats naturally infected with feline leukemia virus (FeLV). AZT was administered subcutaneously at a dose of 5 mg kg-1 body weight every 12 h and PMEA was administered subcutaneously at a dose of 2.5 mg kg-1 body weight every 12 h during a 3 week hospitalization. The therapeutic efficacy of both compounds was investigated. There was a stronger potency of PMEA than of AZT on the regression of stomatitis in FIV and in FeLV infected cats. In addition, in FIV infection PMEA had a stronger effect on the improvement of the general clinical status. Both antiretroviral compounds were potent agents to improve the immunologic status of FIV infected cats by raising the CD4/CD8 ratio. In FeLV infection PMEA and AZT appeared to reduce antigenemia. The hematological side effects caused by PMEA were severe and stronger than those of AZT. Therefore the advantage of PMEA in clinical and immunologic improvement was diminished by the hematologic disorders, which do not allow long term treatment with this drug in the dose used.

Renal biopsy in SLE irrespective of clinical findings: long-term follow-up.

We analyzed data from 56 patients with Systemic Lupus Erythematosus (SLE) in whom renal biopsies were done systematically. The data taken into account for the study were: the histologic glomerular lesions at diagnosis, serum creatinine value, degree of proteinuria and qualitative urine sediment analysis at the time of biopsy, patient age at diagnosis and the evolution of renal function until the time the study was made. Therapy was prescribed according to the glomerular histologic lesion. The mean follow-up period from the time of the first biopsy was 8.2 years. At the time of the study, only 3 patients (5.3%) were on dialysis, while the rest of the patients (94.7%) had a satisfactory renal function. Our results indicate that systematic renal biopsy in SLE patients can furnish valuable data concerning the renal status whether there are clinical signs of renal involvement or not. Treatment based on the histologic images alone may considerably improve renal survival in SLE.

Cobalt-57 bleomycin scanning for lung cancer detection: a prospective study in thoracic surgery.

Patients displaying an abnormal chest X-ray, in some cases, cause a difficult diagnostic problem. A differential diagnosis between benign and malignant lesions is important to determine the choice of treatment i.e. whether or not to perform a thoracotomy. In a prospective study, we have examined the role of 57Co-bleomycin scanning for prethoracotomy assessment of 60 patients with a high clinical probability of lung cancer. For these patients, a sensitivity of 89%, a specificity of 84% and an accuracy of 88% were found. However, as a consequence of the six false-negative scans (two in-situ carcinomas and four stage I carcinomas), bleomycin scanning cannot be regarded as adequate for obviating thoracotomy in patients with a high clinical probability of lung cancer but a negative scan. Nevertheless, the technique is useful for the assessment of tumour size and for the detection of hilar, mediastinal and extra-thoracic metastases, with consequences for TNM staging. It has been found that the tumour dimension correlates well with the actual anatomo-pathologic size determined after surgical examination (r2 = 0.65 and p less than 0.01). Therefore, with an accuracy around 90% for the diagnosis of lung cancer, 57Co-bleomycin scanning offers a major tool for use in clinical investigation.

SPECT study of the fluid distribution in the intra-abdominal space during intraperitoneal treatment of ovarian cancer.

Only limited progress has been achieved in the treatment of ovarian cancer, the most common fatal gynaecological malignancy. Peritoneal dialysis with drugs known to be effective in ovarian cancer and large intraperitoneal fluid volumes (Belly Bath) have been used. The two critical determinants for a successful intraperitoneal chemotherapy programme are: (1) complete accessibility of the drug to all tumour-bearing areas; and (2) drug penetration into the residual tumour masses. We show that the scintigraphic technique in tomographic mode after administration of MAA-99Tcm-containing dialysate is a valuable adjunct for evaluation of patients undergoing intraperitoneal chemotherapy.

Satellite PET and lung cancer: a prospective study in surgical patients.

Positron emission tomography (PET) appears to be an innovative method for imaging the proliferative activity of malignant tissue, in particular by means of 18F-labelled fluorodeoxyglucose (FDG). The potential role of PET scanning was investigated in a satellite centre as an adjunct to conventional methods for estimating the likelihood of pulmonary malignancy. Therefore the sensitivity of detection of lung cancer in candidates was determined prior to exploratory or therapeutic thoracotomy by FDG PET imaging. The study involved 36 patients with abnormal chest roentgenogram and suspected lung cancer who were due for thoracotomy. The PET scans were evaluated qualitatively and semiquantitatively. Pulmonary malignancy was found in 31/36 patients and 29 had a focal increase in FDG pulmonary uptake. Benign pulmonary lesions were found in 5/36 patients, three of whom had a negative PET scan. The sensitivity of detection of lung cancer by FDG PET was therefore 93.5%. Bayesian study shows that FDG PET could be the most useful method in a population with a low prevalence of lung cancer. As illustrated by our study, a simple FDG PET scanning protocol in a satellite PET centre could provide adequate clinical information and help in deciding subsequent patient management.

Modified hamstring musculocutaneous flap for the coverage of ischial pressure sores.

Ischial pressure sores can be efficiently covered with a modification of the traditional V-Y advancement flap, the musculocutaneous hatchet flap. Results of operations performed on 10 patients prove its reliability.