Methane emission from a cool brown dwarf.

Beyond our Solar System, aurorae have been inferred from radio observations of isolated brown dwarfs1,2. Within our Solar System, giant planets have auroral emission with signatures across the electromagnetic spectrum including infrared emission of H3+ and methane. Isolated brown dwarfs with auroral signatures in the radio have been searched for corresponding infrared features, but only null detections have been reported3. CWISEP J193518.59-154620.3. (W1935 for short) is an isolated brown dwarf with a temperature of approximately 482 K. Here we report James Webb Space Telescope observations of strong methane emission from W1935 at 3.326 µm. Atmospheric modelling leads us to conclude that a temperature inversion of approximately 300 K centred at 1-10 mbar replicates the feature. This represents an atmospheric temperature inversion for a Jupiter-like atmosphere without irradiation from a host star. A plausible explanation for the strong inversion is heating by auroral processes, although other internal and external dynamical processes cannot be ruled out. The best-fitting model rules out the contribution of H3+ emission, which is prominent in Solar System gas giants. However, this is consistent with rapid destruction of H3+ at the higher pressure where the W1935 emission originates4.

A planetary collision afterglow and transit of the resultant debris cloud.

Planets grow in rotating disks of dust and gas around forming stars, some of which can subsequently collide in giant impacts after the gas component is removed from the disk1-3. Monitoring programmes with the warm Spitzer mission have recorded substantial and rapid changes in mid-infrared output for several stars, interpreted as variations in the surface area of warm, dusty material ejected by planetary-scale collisions and heated by the central star: for example, NGC 2354-ID8 (refs. 4,5), HD 166191 (ref. 6) and V488 Persei7. Here we report combined observations of the young (about 300 million years old), solar-like star ASASSN-21qj: an infrared brightening consistent with a blackbody temperature of 1,000 Kelvin and a luminosity that is 4 percent that of the star lasting for about 1,000 days, partially overlapping in time with a complex and deep, wavelength-dependent optical eclipse that lasted for about 500 days. The optical eclipse started 2.5 years after the infrared brightening, implying an orbital period of at least that duration. These observations are consistent with a collision between two exoplanets of several to tens of Earth masses at 2-16 astronomical units from the central star. Such an impact produces a hot, highly extended post-impact remnant with sufficient luminosity to explain the infrared observations. Transit of the impact debris, sheared by orbital motion into a long cloud, causes the subsequent complex eclipse of the host star.

Machine learning enables completely automatic tuning of a quantum device faster than human experts.

Variability is a problem for the scalability of semiconductor quantum devices. The parameter space is large, and the operating range is small. Our statistical tuning algorithm searches for specific electron transport features in gate-defined quantum dot devices with a gate voltage space of up to eight dimensions. Starting from the full range of each gate voltage, our machine learning algorithm can tune each device to optimal performance in a median time of under 70 minutes. This performance surpassed our best human benchmark (although both human and machine performance can be improved). The algorithm is approximately 180 times faster than an automated random search of the parameter space, and is suitable for different material systems and device architectures. Our results yield a quantitative measurement of device variability, from one device to another and after thermal cycling. Our machine learning algorithm can be extended to higher dimensions and other technologies.

Molecular mechanism of SHP2 activation by PD-1 stimulation.

In cancer, the programmed death-1 (PD-1) pathway suppresses T cell stimulation and mediates immune escape. Upon stimulation, PD-1 becomes phosphorylated at its immune receptor tyrosine-based inhibitory motif (ITIM) and immune receptor tyrosine-based switch motif (ITSM), which then bind the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2), initiating T cell inactivation. The SHP2-PD-1 complex structure and the exact functions of the two SH2 domains and phosphorylated motifs remain unknown. Here, we explain the structural basis and provide functional evidence for the mechanism of PD-1-mediated SHP2 activation. We demonstrate that full activation is obtained only upon phosphorylation of both ITIM and ITSM: ITSM binds C-SH2 with strong affinity, recruiting SHP2 to PD-1, while ITIM binds N-SH2, displacing it from the catalytic pocket and activating SHP2. This binding event requires the formation of a new inter-domain interface, offering opportunities for the development of novel immunotherapeutic approaches.

Ecosystem engineering by digging mammals: effects on soil fertility and condition in Tasmanian temperate woodland.

Many small- and medium-sized mammals dig for their food. This activity potentially affects soil condition and fertility. Digging is well developed especially in Australian mammals, many of which have recently become rare or extinct. We measured the effects of digging by mammals on soil in a Tasmanian temperate dry sclerophyll forest with an intact mammal community. The density of diggings was 5812 ha-1, affecting 11% of the forest floor. Diggings were created at a rate of around 3113 diggings ha-1 yr-1, disturbing 6.5% of the forest floor and displacing 7.1 m3 ha-1 of soil annually. Most diggings were made by eastern bettongs (Bettongia gaimardi) and short-beaked echidnas (Tachyglossus aculeatus). Many (approx. 30%) fresh diggings consisted of re-excavations of old diggings. Novel diggings displaced 5 m3 ha yr-1 of soil. Diggings acted as traps for organic matter and sites for the formation of new soil, which had higher fertility and moisture content and lower hardness than undisturbed topsoil. These effects on soil fertility and structure were strongest in habitats with dry and poor soil. Creation of fine-scaled heterogeneity by mammals, and amelioration of dry and infertile soil, is a valuable ecosystem service that could be restored by reintroduction of digging mammals to habitats from which they have declined or gone extinct.

Sex-based differential regulation of bacterial-induced bone resorption.

BACKGROUND AND OBJECTIVE: Periodontal disease pathogenesis is comprised of the complex inflammatory immune response to oral bacterial dysbiosis. Like other inflammatory diseases, there is sexual dimorphism evident in periodontal diseases. During periodontitis, inflammatory chemokines direct neutrophils to migrate to the site of infection to neutralize the pathogen. Interestingly, these same chemokines are also involved in regulating pathogen-induced osteoclast formation. Previous reports show differences in bone turnover and lymphocyte recruitment between sexes. We hypothesize that chemokine expression is differentially regulated by sex and thus results in differential osteoclast formation. MATERIAL AND METHODS: Male and female mice were utilized to isolate neutrophils based on expression of Ly6G-specific, as well as defined osteoclast progenitors. Cells were stimulated with lipopolysaccharide (LPS; 100 ng/mL) then analyzed for neutrophil infiltration and gene expression. Defined osteoclast progenitors were primed: macrophage-colony stimulating factor (25 ng/mL), receptor activator of NF-κB ligand (50 ng/mL), then stimulated with LPS. Osteoclasts were enumerated via TRAP stain and mRNA isolated for gene expression analysis via quantitative polymerase chain reaction. RESULTS: In response to LPS, male neutrophils in vitro respond with increased chemokine expression and significantly more osteoclast formed in response to LPS compared to females. CONCLUSIONS: Findings support observations in humans regarding a sexual dimorphism in oral bacterial infections of alveolar bone loss. Males have a strong inflammatory response to bacterial infection, resulting in increased inflammatory microenvironment, reduced pathogenic bacteria clearance and increased osteoclast-driven bone loss in response to differential expression of key chemokines.

The horseshoe kidney: Surgical anatomy and embryology.

Horseshoe kidneys are a common, yet enigmatic, renal malformation. This review critically appraised the literature surrounding the embryology, etiology and clinical anatomy of horseshoe kidneys. The systematic literature search produced 104 articles, and 56 primary and further secondary references. There were several etiological theories regarding horseshoe kidneys. The established view was that during ascent, the kidneys come into close apposition as they pass through an arterial fork. Another possible mechanism related to lateral flexion of the trunk or rotation of the caudal embryo; the association of asymmetrical horseshoe kidneys with a number of vertebral conditions supported this hypothesis. More recent animal models implicated the notochord and sonic hedgehog signaling. Furthermore, it has been suggested that the isthmus may be the result of ectopic mesenchymal tissue. Surgical anatomy of the horseshoe kidney is complex, due to variability in location, orientation and blood supply. Both arterial and venous anatomy is highly variable. This raised the question of whether anomalous blood supply is the cause or result of abnormal renal position. In the majority of cases, the isthmus contained functional renal parenchyma. In over 90% of cases, fusion between the kidneys occurred at the lower pole. Despite commonly being quoted as 'held back by the inferior mesenteric artery' at L3, in reality the isthmus was only found immediately inferior to this in 40% of cases.

Broad-scale impacts of salmon farms on temperate macroalgal assemblages on rocky reefs.

Intensive fish culture in open sea pens delivers large amounts of nutrients to coastal environments. Relative to particulate waste impacts, the ecological impacts of dissolved wastes are poorly known despite their potential to substantially affect nutrient-assimilating components of surrounding ecosystems. Broad-scale enrichment effects of salmonid farms on Tasmanian reef communities were assessed by comparing macroalgal cover at four fixed distances from active fish farm leases across 44 sites. Macroalgal assemblages differed significantly between sites immediately adjacent (100m) to fish farms and reference sites at 5km distance, while sites at 400m and 1km exhibited intermediate characteristics. Epiphyte cover varied consistently with fish farm impacts in both sheltered and exposed locations. The green algae Chaetomorpha spp. predominated near fish farms at swell-exposed sites, whereas filamentous green algae showed elevated densities near sheltered farms. Cover of canopy-forming perennial algae appeared unaffected by fish farm impacts.

Which visual acuity measurements define high-quality care for patients with neovascular age-related macular degeneration treated with ranibizumab?

PURPOSE: The purpose of this study is to define which visual acuity (VA) measurements are the best indicators of high-quality care for patients receiving intravitreal ranibizumab for neovascular age-related macular degeneration (nAMD). METHODS: Analysis of prospectively collected data recorded within an electronic medical record system on treatment-naive, first-eligible eyes with nAMD, treated with ranibizumab using an as-needed treatment regimen with a minimum follow-up of 1 year. Data collection included the following: age, gender, laterality, type of nAMD, VA, central 1 mm OCT retinal thickness, number of intravitreal injections, and number of follow-up assessments. RESULTS: Data were available on the first-treated eye from 406 patients with at least 1 year follow-up; of these, 198 had data at 2 years. The mean baseline VA of 54.4 Early Treatment Diabetic Retinopathy Study letters improved to 58.5 letters at 12 months and to 56.8 letters at 24 months. The mean VA changes from baseline to 1 year were +6.5, +7.5, +1.7, and -1.5 letters, respectively, for baseline VA categories of 23-35, 36-55, 56-70, and >70 letters. Change in mean VA from the end of the loading phase to year 1 ranged from -2.9 to +1.4 letters for the different baseline VA categories. The mean number of injections were similar across baseline VA categories ranging from 5.7 to 6.0 injections in year 1 and from 3.3 to 3.8 in year 2. CONCLUSIONS: This large, real-world series demonstrates that mean change in VA is largely a function of selection criteria and baseline VA. The quality of a service is therefore better judged by actual VA outcomes and maintenance of vision after the loading phase.

Stereotactic radiotherapy for malignancies involving the trigeminal and facial nerves.

Involvement of a cranial nerve caries a poor prognosis for many malignancies. Recurrent or residual disease in the trigeminal or facial nerve after primary therapy poses a challenge due to the location of the nerve in the skull base, the proximity to the brain, brainstem, cavernous sinus, and optic apparatus and the resulting complex geometry. Surgical resection caries a high risk of morbidity and is often not an option for these patients. Stereotactic radiosurgery and radiotherapy are potential treatment options for patients with cancer involving the trigeminal or facial nerve. These techniques can deliver high doses of radiation to complex volumes while sparing adjacent critical structures. In the current study, seven cases of cancer involving the trigeminal or facial nerve are presented. These patients had unresectable recurrent or residual disease after definitive local therapy. Each patient was treated with stereotactic radiation therapy using a linear accelerator based system. A multidisciplinary approach including neuroradiology and surgical oncology was used to delineate target volumes. Treatment was well tolerated with no acute grade 3 or higher toxicity. One patient who was reirradiated experienced cerebral radionecrosis with mild symptoms. Four of the seven patients treated had no evidence of disease after a median follow up of 12 months (range 2-24 months). A dosimetric analysis was performed to compare intensity modulated fractionated stereotactic radiation therapy (IM-FSRT) to a 3D conformal technique. The dose to 90% (D90) of the brainstem was lower with the IM-FSRT plan by a mean of 13.5 Gy. The D95 to the ipsilateral optic nerve was also reduced with IM-FSRT by 12.2 Gy and the D95 for the optic chiasm was lower with FSRT by 16.3 Gy. Treatment of malignancies involving a cranial nerve requires a multidisciplinary approach. Use of an IM-FSRT technique with a micro-multileaf collimator resulted in a lower dose to the brainstem, optic nerves and chiasm for each case examined.

Arterial injuries at the elbow carry a high risk of muscle necrosis and warrant urgent revascularisation.

INTRODUCTION: Revascularisation following axial arterial system injury is effective in upper limb salvage but necrosis of muscle, the tissue most sensitive to ischaemia, may still occur. We examined the frequency of necrosis, its related factors and its functional significance. METHODS: The clinical findings and operative management of 13 patients with injuries at the elbow referred to 2 plastic surgical hand surgery units over a 30-month period were reviewed. Good outcome was defined as minimal impairment with return to previous occupation, intermediate outcome as moderate impairment with change in occupation and poor outcome as major functional loss preventing work. RESULTS: Seven patients injured the brachial and six injured both the radial and ulnar arteries. Concomitant injuries were severe with nerve injuries in 11 and muscle damage in 12 patients. Functional outcome was good in four cases, intermediate in four and poor in five. Muscle necrosis developed in four brachial artery injuries. In all four cases, initial successful revascularisation failed post-operatively. Case review revealed delayed recognition in three cases where pain heralded ischaemia but distal skin circulation and pulses were adequate. Of patients with necrosis, three had a poor outcome and one had an intermediate outcome. CONCLUSIONS: The risk of muscle necrosis must be considered when managing these injuries, particularly if initial revascularisation is unsuccessful. Every effort should be made to optimise repair technique and post-operative monitoring. Limb salvage is no longer enough. Fully viable muscle is necessary to restore function and livelihoods.

TU-E-BRB-09: Validation of Multi-Focal Stereotactic Radiosurgery with Volumetric Modulated Arc Therapy with High-Resolution 3D Dosimetry.

PURPOSE: Volumetric modulated arc therapy (VMAT) enables stereotactic radiosurgery (SRS) treatment for multiple lesions with a single isocenter setup. Dosimetry verification is highly challenging however, and the purpose of this study is to validate this new treatment using novel 3D dosimetry techniques, with potential for dramatically more comprehensive verification than possible with conventional approaches. METHODS: A cylindrical PRESAGE dosimeter was inserted into an RPC type head phantom for treatment validation. The phantom was immobilized with an SRS U-frame system and a set of simulation CT images was acquired with a SRS localizer. A 5-arc VMAT multi-focal SRS plan was created to treat 5 intracranial lesions simultaneously. A set of cone-beam CT (CBCT) images was then acquired to localize the isocenter, and the VMAT plan delivered to the combined phantom. The PRESAGE dosimeter was then removed and scanned by optical-computed-tomography (optical-CT). The 3D PRESAGE dose measurement was reconstructed with 1 mm resolution. Another PRESAGE insert with a pre-drilled ion chamber channel was placed in the phantom and an SRS ion chamber was mounted for an absolute dose measurement. The phantom was again localized with CBCT and the VMAT plan was delivered. The dose measured with the ion chamber was compared with calculated dose. RESULTS: The mean planned and PRESAGE measured doses to target 1 were 12.1Gy and 12.2 Gy, 18.7 Gy and 18.5 Gy for target 2, 18.6 Gy and 18.4 Gy for target 3, 15.5 Gy and 15.4 Gy for target 4, 18.7 Gy and 19.0 Gy for target 5. The 3D gamma passing rate was 95.6% for 3% and 1mm. The ion chamber measured dose was within 1% of the planned dose. CONCLUSIONS: Our 3D PRESAGE dose measurement shows that multi-focal VMAT is a valid technique for single isocenter SRS treatment of multiple lesions. This research is partially supported by NCI R01CA100835. This research is partially supported by NCI R01CA100835.

SU-E-T-645: Treatment of Multiple Brain Metastases Using Stereotactic Radiosurgery with Single-Isocenter Volumetric Modulated Arc Therapy: Comparison with Conventional Dynamic Conformal Arc and Static Beam Stereotactic Radiosurgery.

PURPOSE: To investigate the treatment of multiple brain metastases using stereotactic radiosurgery with single-isocenter volumetric modulated arc therapy (VMAT) compared with conventional multi-isocenter dynamic conformal arc therapy (DCAT) and three-dimensional conformal radiation therapy (3D-CRT). METHODS: Seventeen patients with 2 to 5 brain metastatic lesions were studied. The number of patients with 5, 4, 3, and 2 lesions were 4, 5, 4, and 4, respectively. For patients treated with DCAT/3D-CRT plans, VMAT plans were retrospectively generated, and vice versa. Single-isocenter set up was employed in VMAT plans while the number of isocenters was proportional to the number of lesions in DCAT/3D-CRT plans. The DCAT/3D-CRT and VMAT plans were generated using iPlan® RT Dose Version 4.1.1 (BrainLAB, Germany) and Eclipse™ Version 8.6 (Varian, USA) treatment planning system, respectively. All plans were designed to be delivered on Novalis Tx™ system (Varian, USA and BrainLAB, Germany), in which the accelerator equipped with a high definition multileaf collimator (HDMLC). RESULTS: Conformity index for VMAT plans were equivalent to or better than that for DCAT/3D-CRT plans. While VMAT and DCAT/3D-CRT plans were similar in target coverage, quality of coverage for VMAT plans was better. However, the volume receiving 5Gy was 46% larger for VMAT plans. In addition, the distance from individual lesion to the VMAT isocenter has no impact on VMAT plans. Compared with DCAT/3D-CRT plans, the mean monitor units (MU) decreased by 42% and the estimated treatment time decreased by 49% for VMAT plans. CONCLUSIONS: This work suggests that single-isocenter VMAT is promising for stereotactic radiosurgery in the treatment of multiple brain metastases. Single-isocenter VMAT is able to achieve comparable conformity, target coverage and quality of coverage with significantly superior delivery efficiency.

Impact of logging on aboveground biomass stocks in lowland rain forest, Papua New Guinea.

Greenhouse-gas emissions resulting from logging are poorly quantified across the tropics. There is a need for robust measurement of rain forest biomass and the impacts of logging from which carbon losses can be reliably estimated at regional and global scales. We used a modified Bitterlich plotless technique to measure aboveground live biomass at six unlogged and six logged rain forest areas (coupes) across two approximately 3000-ha regions at the Makapa concession in lowland Papua New Guinea. "Reduced-impact logging" is practiced at Makapa. We found the mean unlogged aboveground biomass in the two regions to be 192.96 +/- 4.44 Mg/ha and 252.92 +/- 7.00 Mg/ha (mean +/- SE), which was reduced by logging to 146.92 +/- 4.58 Mg/ha and 158.84 +/- 4.16, respectively. Killed biomass was not a fixed proportion, but varied with unlogged biomass, with 24% killed in the lower-biomass region, and 37% in the higher-biomass region. Across the two regions logging resulted in a mean aboveground carbon loss of 35 +/- 2.8 Mg/ha. The plotless technique proved efficient at estimating mean aboveground biomass and logging damage. We conclude that substantial bias is likely to occur within biomass estimates derived from single unreplicated plots.

Estimating rainforest biomass stocks and carbon loss from deforestation and degradation in Papua New Guinea 1972-2002: Best estimates, uncertainties and research needs.

Reduction of carbon emissions from tropical deforestation and forest degradation is being considered a cost-effective way of mitigating the impacts of global warming. If such reductions are to be implemented, accurate and repeatable measurements of forest cover change and biomass will be required. In Papua New Guinea (PNG), which has one of the world's largest remaining areas of tropical forest, we used the best available data to estimate rainforest carbon stocks, and emissions from deforestation and degradation. We collated all available PNG field measurements which could be used to estimate carbon stocks in logged and unlogged forest. We extrapolated these plot-level estimates across the forested landscape using high-resolution forest mapping. We found the best estimate of forest carbon stocks contained in logged and unlogged forest in 2002 to be 4770 Mt (+/-13%). Our best estimate of gross forest carbon released through deforestation and degradation between 1972 and 2002 was 1178 Mt (+/-18%). By applying a long-term forest change model, we estimated that the carbon loss resulting from deforestation and degradation in 2001 was 53 Mt (+/-18%), rising from 24 Mt (+/-15%) in 1972. Forty-one percent of 2001 emissions resulted from logging, rising from 21% in 1972. Reducing emissions from logging is therefore a priority for PNG. The large uncertainty in our estimates of carbon stocks and fluxes is primarily due to the dearth of field measurements in both logged and unlogged forest, and the lack of PNG logging damage studies. Research priorities for PNG to increase the accuracy of forest carbon stock assessments are the collection of field measurements in unlogged forest and more spatially explicit logging damage studies.

The practical side of immunocontraception: zona proteins and wildlife.

With shrinking habitat, the humane control of certain wildlife populations is relevant. The contraceptive vaccine based on native porcine zona pellucida (PZP) has been applied to various wildlife populations for 20 years. Prominent efforts include wild horses, urban deer, zoo animals and African elephants, among others. This approach has been successful in managing entire populations and to date, no significant debilitating short- or long-term health effects have been documented.

"Gearing to a time table"; the evolution of earlier surgical eschar excision in massive burns by British burns surgeons at the battles of Cassino, 1944: an example of real-time audit.

The effectiveness of burns care delivery is difficult to measure within a realistic workload and resource framework. In addition, workers must develop new tools for this purpose. We describe a historical example from World War II describing the evolution of burns excision in the context of thorough outcome assessment, during the allied advance from North Africa up the Italian peninsular, including the battles of Cassino 1942-1945. Patrick Clarkson and Rex Lawrie working as plastic surgeons in a small forward Maxillofacial Unit were able to fully assess the management and outcome of 800 burnt servicemen. 192 burns were full thickness and required grafting. Prospective data revealed that those burns which were surgically excised and grafted between 12 and 18 days recovered more quickly than those managed by conservative dressings until the eschar had sloughed off followed by grafting. Burns managed by excision and grafting in less than 5 weeks following burning (n=86) healed 8.6 days faster than those grafted later (n=106). This difference was increased for massive burns of over 1000 cm(2), with those grafted in less than 5 weeks (n=17) healing 13 days faster than the delayed group (n=27). Their transparent and simple method of prospective audit is described.