Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.

Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.

SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.

Discovery of Gamma Rays from the Quiescent Sun with HAWC.

We report the first detection of a TeV γ-ray flux from the solar disk (6.3σ), based on 6.1 years of data from the High Altitude Water Cherenkov (HAWC) observatory. The 0.5-2.6 TeV spectrum is well fit by a power law, dN/dE=A(E/1 TeV)^{-γ}, with A=(1.6±0.3)×10^{-12} TeV^{-1} cm^{-2} s^{-1} and γ=3.62±0.14. The flux shows a strong indication of anticorrelation with solar activity. These results extend the bright, hard GeV emission from the disk observed with Fermi-LAT, seemingly due to hadronic Galactic cosmic rays showering on nuclei in the solar atmosphere. However, current theoretical models are unable to explain the details of how solar magnetic fields shape these interactions. HAWC's TeV detection thus deepens the mysteries of the solar-disk emission.

PHEOCHROMOCYTOMA, THE GREAT MASQUERADER, PRESENTING AS REVERSIBLE CARDIOMYOPATHY: PRIMUM NON NOCERE.

Background: Pheochromocytoma, the great masquerader, can have a varied spectrum of clinical manifestations. It can often cause a diagnostic challenge despite the availability of modern investigation modalities. Case: We present the case of a 38-year-old male who presented with uncontrolled hypertension for the past 10 years and heart failure for one year. The diagnosis of pheochromocytoma was missed in the initial setting, leading to a biopsy of the retroperitoneal mass. Fortunately, the patient survived the procedure. Subsequently, with the involvement of a multi-disciplinary team, he was optimized for surgery under strict cardiac monitoring. After the complete excision of the tumour, he showed significant improvement not only in his clinical symptoms but also in his cardiac status. Conclusions: This case emphasizes the age-old medical phrase of 'Primum non nocere or first, do no harm'. Any invasive procedure in a pheochromocytoma can lead to a massive release of catecholamines causing a hypertensive crisis, pulmonary oedema, and even cardiac arrest. Any young patient presenting with hypertension or heart failure should be investigated for secondary causes. Cardiomyopathy due to pheochromocytoma is because of catecholamine overload and usually reverses or improves after curative surgery.

ITSN1 regulates SAM68 solubility through SH3 domain interactions with SAM68 proline-rich motifs.

SAM68 is an mRNA-binding protein involved in mRNA processing in the nucleus that forms membraneless compartments called SAM68 Nuclear Bodies (SNBs). We found that intersectin 1 (ITSN1), a multidomain scaffold protein harboring five soluble SH3 domains, interacts with SAM68 proline-rich motifs (PRMs) surrounded by self-adhesive low complexity domains. While SAM68 is poorly soluble in vitro, the interaction of ITSN1 SH3 domains and mRNA with SAM68 enhances its solubility. In HeLa cells, the interaction between the first ITSN1 SH3 domain (SH3A) and P0, the N-terminal PRM of SAM68, induces the dissociation of SNBs. In addition, we reveal the ability of another SH3 domain (SH3D) of ITSN1 to bind to mRNAs. ITSN1 and mRNA may thus act in concert to promote SAM68 solubilization, consistent with the absence of mRNA in SNBs in cells. Together, these results support the notion of a specific chaperoning of PRM-rich SAM68 within nuclear ribonucleoprotein complexes by ITSN1 that may regulate the processing of a fraction of nuclear mRNAs, notably SAM68-controlled splicing events related to higher neuronal functions or cancer progression. This observation may also serve as a putative model of the interaction between other PRM-rich RBPs and signaling proteins harboring SH3 domains.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

The expanding fireball of Nova Delphini 2013.

A classical nova occurs when material accreting onto the surface of a white dwarf in a close binary system ignites in a thermonuclear runaway. Complex structures observed in the ejecta at late stages could result from interactions with the companion during the common-envelope phase. Alternatively, the explosion could be intrinsically bipolar, resulting from a localized ignition on the surface of the white dwarf or as a consequence of rotational distortion. Studying the structure of novae during the earliest phases is challenging because of the high spatial resolution needed to measure their small sizes. Here we report near-infrared interferometric measurements of the angular size of Nova Delphini 2013, starting one day after the explosion and continuing with extensive time coverage during the first 43 days. Changes in the apparent expansion rate can be explained by an explosion model consisting of an optically thick core surrounded by a diffuse envelope. The optical depth of the ejected material changes as it expands. We detect an ellipticity in the light distribution, suggesting a prolate or bipolar structure that develops as early as the second day. Combining the angular expansion rate with radial velocity measurements, we derive a geometric distance to the nova of 4.54 ± 0.59 kiloparsecs from the Sun.

Volumetric laser endomicroscopy and its application to Barrett's esophagus: results from a 1,000 patient registry.

Volumetric laser endomicroscopy (VLE) uses optical coherence tomography (OCT) for real-time, microscopic cross-sectional imaging. A US-based multi-center registry was constructed to prospectively collect data on patients undergoing upper endoscopy during which a VLE scan was performed. The objective of this registry was to determine usage patterns of VLE in clinical practice and to estimate quantitative and qualitative performance metrics as they are applied to Barrett's esophagus (BE) management. All procedures utilized the NvisionVLE Imaging System (NinePoint Medical, Bedford, MA) which was used by investigators to identify the tissue types present, along with focal areas of concern. Following the VLE procedure, investigators were asked to answer six key questions regarding how VLE impacted each case. Statistical analyses including neoplasia diagnostic yield improvement using VLE was performed. One thousand patients were enrolled across 18 US trial sites from August 2014 through April 2016. In patients with previously diagnosed or suspected BE (894/1000), investigators used VLE and identified areas of concern not seen on white light endoscopy (WLE) in 59% of the procedures. VLE imaging also guided tissue acquisition and treatment in 71% and 54% of procedures, respectively. VLE as an adjunct modality improved the neoplasia diagnostic yield by 55% beyond the standard of care practice. In patients with no prior history of therapy, and without visual findings from other technologies, VLE-guided tissue acquisition increased neoplasia detection over random biopsies by 700%. Registry investigators reported that VLE improved the BE management process when used as an adjunct tissue acquisition and treatment guidance tool. The ability of VLE to image large segments of the esophagus with microscopic cross-sectional detail may provide additional benefits including higher yield biopsies and more efficient tissue acquisition. Clinicaltrials.gov NCT02215291.

Spastin regulates VAMP7-containing vesicles trafficking in cortical neurons.

Alteration of axonal transport has emerged as a common precipitating factor in several neurodegenerative disorders including Human Spastic Paraplegia (HSP). Mutations of the SPAST (SPG4) gene coding for the spastin protein account for 40% of all autosomal dominant uncomplicated HSP. By cleaving microtubules, spastin regulates several cellular processes depending on microtubule dynamics including intracellular membrane trafficking. Axonal transport is fundamental for the viability of motor neurons which often have very long axons and thus require efficient communication between the cell body and its periphery. Here we found that the anterograde velocity of VAMP7 vesicles, but not that of VAMP2, two vesicular-SNARE proteins implicated in neuronal development, is enhanced in SPG4-KO neurons. We showed that this effect is associated with a slight increase of the level of acetylated tubulin in SPG4-KO neurons and correlates with an enhanced activity of kinesin-1 motors. Interestingly, we demonstrated that an artificial increase of acetylated tubulin by drugs reproduces the effect of Spastin KO on VAMP7 axonal dynamics but also increased its retrograde velocity. Finally, we investigated the effect of microtubule targeting agents which rescue axonal swellings, on VAMP7 and microtubule dynamics. Our results suggest that microtubule stabilizing agents, such as taxol, may prevent the morphological defects observed in SPG4-KO neurons not simply by restoring the altered anterograde transport to basal levels but rather by increasing the retrograde velocity of axonal cargoes.

Th1/Th2 immune responses and oxidative stress in caprine flea allergy dermatitis.

Flea allergy dermatitis (FAD) is the common, often neglected skin disease of goats caused mainly by Ctenocephalides felis. This study aimed to evaluate the immuno-oxidative pathobiology of FAD in goats. Twelve goats from the same herd were divided into two groups of six animals each. The group I (FAD) included animals with natural flea infestation and severe dermatitis lesions. The group II (Healthy control) animals were free from any parasitic infestation. To assess the pathological changes, the markers of oxidative stress (lipid peroxidation, reduced glutathione and total antioxidant capacity), and immune status (Tumour necrosis factor alpha, Interleukin 10, Transforming growth factor beta 1 and Th1/Th2 cytokine ratio) were evaluated from the blood and the serum samples. Remarkable oxidative stress and severe inflammatory response with Th2 cytokine dominance were observed in flea infested animals. Highly antigenic agents of fleas, either secretory or excretory or structural, induced severe inflammatory responses and significant oxidative stress in caprine FAD. Massive release of cytokines may be responsible for severe skin inflammation and lesions in FAD in contrast to other Th2 dominant ectoparasitic skin conditions of goats'.

Comparative analysis of midgut bacterial communities in three aedine mosquito species from dengue-endemic and non-endemic areas of Rajasthan, India.

Dengue viruses are transmitted to humans through the bites of infected female aedine mosquitoes. Differences in the composition and structure of bacterial communities in the midguts of mosquitoes may affect the vector's ability to transmit the disease. To investigate and analyse the role of midgut bacterial communities in viral transmission, midgut bacteria from three species, namely Stegomyia aegypti (= Aedes aegypti), Fredwardsius vittatus (= Aedes vittatus) and Stegomyia albopicta (= Aedes albopictus) (all: Diptera: Culicidae), from dengue-endemic and non-endemic areas of Rajasthan, India were compared. Construction and analyses of six 16S rRNA gene libraries indicated that Serratia spp.-related phylotypes dominated all clone libraries of the three mosquito species from areas in which dengue is not endemic. In dengue-endemic areas, phylotypes related to Aeromonas, Enhydrobacter spp. and uncultivated bacterium dominated the clone libraries of S. aegypti, F. vittatus and S. albopicta, respectively. Diversity indices analysis and real-time TaqMan polymerase chain reaction assays showed bacterial diversity and abundance in the midguts of S. aegypti to be higher than in the other two species. Significant differences observed among midgut bacterial communities of the three mosquito species from areas in which dengue is and is not endemic, respectively, may be related to the vectorial capacity of mosquitoes to carry dengue viruses and, hence, to the prevalence of disease in some areas.

Cost analysis of gentamicin-impregnated collagen sponges in preventing sternal wound infection post cardiac surgery.

OBJECTIVE: The use of antibiotic-impregnated sponges (Collatamp) during cardiac surgery is controversial. We analysed the cost-effectiveness of its selective use in patients at high-risk of sternal wound infection (SWI). METHOD: Postoperative costs were analysed in two groups of patients undergoing heart surgery between 2011 and 2013: those with SWI (group 1) and in high-risk patients without SWI (group 2). The potential cost of gentamicin-impregnated collagen sponges (GCS) use in high-risk patients was compared with our current practice. RESULTS: We identified 1,251 patients with at least one recognised risk factor for developing SWI in this period. Of these, 18 developed SWI (incidence 1.4%). The median postoperative cost per patient without SWI was £9,617. The additional cost per patient incurred by SWI was £4,860.75. The annual additional cost for treating patients with SWI was £43,749. With a 50% reduction in SWI, the annual additional cost of treating these patients would be reduced to £21,873. The cost of GCS is £80 per patient. Adding this to £21,873 gives a potential total cost of £71,913 in the treated high-risk cohort. CONCLUSION: In our practice the annual cost of treating SWI in high-risk patients without use of GCS is lower than the annual cost of using GCS in all high-risk patients (£43,749 versus £71,913) if it produces a 50% reduction in SWI. The reduction in the incidence of SWI poses no economic benefit when the cost of the product is factored in.

Recent Advances in Psoriatic Arthritis from Obscurity to Prominence.

Psoriatic arthritis is a fascinating inflammatory arthritis. Till recently it did not generate interest for lack of understanding of its immunopathology, and lack of effective treatment. This has changed. PsA is now one of the hot topics - all due to elucidation of genetic susceptibility associations, immunopathogenesis and availability of effective therapy. In this communication we provide an overview of these aspects of psoriatic arthritis.

Application of response surface methodology in optimization of lactic acid fermentation of radish: effect of addition of salt, additives and growth stimulators.

Lactic acid fermentation of radish was conducted using various additive and growth stimulators such as salt (2 %-3 %), lactose, MgSO4 + MnSO4 and Mustard (1 %, 1.5 % and 2 %) to optimize the process. Response surface methodology (Design expert, Trial version 8.0.5.2) was applied to the experimental data for the optimization of process variables in lactic acid fermentation of radish. Out of various treatments studied, only the treatments having ground mustard had an appreciable effect on lactic acid fermentation. Both linear and quadratic terms of the variables studied had a significant effect on the responses studied. The interactions between the variables were found to contribute to the response at a significant level. The best results were obtained in the treatment with 2.5 % salt, 1.5 % lactose, 1.5 % (MgSO4 + MnSO4) and 1.5 % mustard. These optimized concentrations increased titrable acidity and LAB count, but lowered pH. The second-order polynomial regression model determined that the highest titrable acidity (1.69), lowest pH (2.49) and maximum LAB count (10 × 10(8) cfu/ml) would be obtained at these concentrations of additives. Among 30 runs conducted, run 2 has got the optimum concentration of salt- 2.5 %, lactose- 1.5 %, MgSO4 + MnSO4- 1.5 % and mustard- 1.5 % for lactic acid fermentation of radish. The values for different additives and growth stimulators optimized in this study could successfully be employed for the lactic acid fermentation of radish as a postharvest reduction tool and for product development.

Effect of pre-treatments and drying methods on quality attributes of sweet bell-pepper (Capsicum annum) powder.

Pre-treatments and methods of drying for producing good quality dried bell pepper powder for use in the ready-to-eat (RTE) food products were optimized. Out of various pre-treatments used (blanching in boiling water, KMS, CA and combination of KMS + CA at different concentrations), soaking of bell pepper shreds in KMS@ 0.20 % + CA@ 0.50 % after blanching fasten the drying process (19.75 h) compared to control (22.60 h), when dried in mechanical dehydrator at 58 ± 2 °C. Blanching prior to drying improved the rate of drying and produced product with lower acidity (1.25 %). The samples (T7) treated with KMS@ 0.20 % + CA@ 0.50 % significantly (p < 0.05) retained the ascorbic acid content (47.75 mg/100 g) and also attained highest score for colour (8.0), texture (7.5) and overall acceptability (7.5) compared to rest of the treatments. Among different methods of drying, pre-treated bell peppers dried in solar poly tunnel drier produced bright red coloured powder with relatively higher amounts of sugars and ascorbic acid content, hence was optimized. Visual lump formation was observed at 19.75 % and 18.50 % critical moisture contents, which equilibrated at 42 % and 45 % RH for bell pepper powders dried in a mechanical dehydrator and solar poly tunnel drier, respectively.

Severe life-threatening Ehrlichia chaffeensis infections transmitted through solid organ transplantation.

BACKGROUND: Donor-derived infections from organ transplantation are rare occurrences with preoperative screening practices. Ehrlichia chaffeensis, a tick-borne illness, transmitted through solid organ transplantation has not been reported previously to our knowledge. We present cases of 2 renal allograft recipients who developed severe E. chaffeensis infection after receipt of organs from a common deceased donor. METHODS: The 2 renal transplant patients who developed E. chaffeensis infection are reported in case study format with review of the literature. RESULTS: Approximately 3 weeks after renal transplantation, both patients developed an acute febrile illness and rapid clinical decline. Recipient A underwent an extensive infectious workup that revealed positive E. chaffeensis DNA from polymerase chain reaction on peripheral blood. Recipient B's clinical team obtained acute and convalescent antibody titers for E. chaffeensis, which demonstrated acute infection. Recipients A and B were treated with doxycycline and tigecycline, respectively, with clinical cure. CONCLUSIONS: These cases demonstrate that tick-borne pathogens, such as E. chaffeensis, can be transmitted through renal transplantation. E. chaffeensis can be associated with excessive morbidity and mortality, commonly owing to delay in diagnosis and poor response to non-tetracycline antibiotics. In populations with endemic tick-borne illness, donors should be questioned about tick exposure, and appropriate antibiotics can be administered if indicated.

Anatomy of undiagnosed fever--a physician's perspective.

Undiagnosed fever is a vexing problem. The reasons why fever remains undiagnosed can be inherent to the underlying pathology, our shortcoming(s) or both. This article describes "our" causes based on cases seen over the years. It is apparent that with proper attention to details mystery of at least some undiagnosed fevers can be solved.

Value addition of wild apricot fruits grown in North-West Himalayan regions-a review.

Wild apricot (Prunus armeniaca L.) commonly known as chulli is a potential fruit widely distributed in North-West Himalayan regions of the world. The fruits are good source of carbohydrates, vitamins, minerals besides having attractive colour and typical flavour. Unlike table purpose varieties of apricots like New Castle, the fruits of wild apricot are unsuitable for fresh consumption because of its high acid and low sugar content. However, the fruits are traditionally utilized for open sun drying, pulping to prepare different products such as jams, chutney and naturally fermented and distilled liquor. But, scientific literature on processing and value addition of wild apricot is scanty. Preparation of jam with 25 % wild apricot +75 % apple showed maximum score for organoleptic characteristics due to better taste and colour. Osmotic dehydration has been found as a suitable method for drying of wild type acidic apricots. A good quality sauce using wild apricot pulp and tomato pulp in the ratio of 1:1 has been prepared, while chutney of good acceptability prepared from wild apricot pulp (100 %) has also been documented. Preparation of apricot-soy protein enriched products like apricot-soya leather, toffee and fruit bars has been reported, which are reported to meet the protein requirements of adult and children as per the recommendations of ICMR. Besides these processed products, preparation of alcoholic beverages like wine, vermouth and brandy from wild apricot fruits has also been reported by various researchers. Further, after utilization of pulp for preparation of value added products, the stones left over have been successfully utilized for oil extraction which has medicinal and cosmetic value. The traditional method of oil extraction has been reported to be unhygienic and result in low oil yield with poor quality, whereas improved mechanical method of oil extraction has been found to produce good quality oil. The apricot kernel oil and press cake have successfully been utilized for preparation of various value added products such as facial cream, lip balm, essential oil and protein isolate with good quality attributes and consumer acceptability. However, no scientific information on utilization of shells remained after kernel separation is available, but the shells are traditionally utilized for burning purpose during winters by the farmers. Therefore, it seems that every part of wild apricot can be utilized for conversion into value-added products and commercial utilization of this fruit will certainly add value to this underutilized fruit and also increase the economy of farmers.

The need for thoracic surgery in adult patients receiving extracorporeal membrane oxygenation: a 16-year experience.

OBJECTIVES: Patients on extracorporeal membrane oxygenation (ECMO) are at risk from thoracic complications such as bleeding or pneumothorax, which may subsequently necessitate thoracic surgical intervention. We aimed to: 1) analyse the indication and nature of thoracic surgical intervention in these patients and 2) analyse the effect of a change in the ECMO circuit from roller pump to centrifugal pump on transfusion requirements pre and post thoracotomy. METHODS: We retrospectively reviewed a prospectively collected database of 569 adults put on ECMO between 1995 and 2011. Patients undergoing thoracotomy were identified and outcomes were statistically analysed. RESULTS: Forty thoracotomies were performed in 18 patients [61% male, median age 31 (14-56) years, one bilateral procedure]. The indications for ECMO included: pneumonia 14/18 (78%), trauma 2/18 (11%) and other 2/18 (11%). Median duration on ECMO was 13 (1-257) days and the time to initial thoracotomy was 10 (1-183) days. The indications for thoracotomy were: excessive bleeding post chest drain insertion (11/19, 58%), uncontrolled air leak (9/19, 47%) and pleural effusion (4/19, 21%). The primary operations were 12/19 (63%) evacuation of haemothorax, 3/19 (16%) lung repair, 2/19 (11%) diagnostic lung biopsy and 2/19 (11%) other. Ten patients needed a further 21 thoracotomies (3 lobectomies); average 2 (1-5) per patient. In total, 30/40 (75%) thoracotomies were performed for bleeding complication. The change from roller to centrifugal pump trended towards a reduction in mean transfusion requirements in these patients following thoracotomy (11.5 versus 4 units, p=0.14). The in-hospital mortality was 7/18 (39%) patients. There were no statistically significant predictors of poor outcome. CONCLUSIONS: The need for thoracotomy whilst on ECMO is 3.2% in this large series. Intervention may be complicated, thus, either ECMO specialists should have thoracic training or thoracic surgeons should be on-site. Potential mortality is high and, although not statistically significant, a difference in transfusion requirements was observed following the change of circuit.