A brief visit from a red and extremely elongated interstellar asteroid.

None of the approximately 750,000 known asteroids and comets in the Solar System is thought to have originated outside it, despite models of the formation of planetary systems suggesting that orbital migration of giant planets ejects a large fraction of the original planetesimals into interstellar space. The high predicted number density of icy interstellar objects (2.4 × 10-4 per cubic astronomical unit) suggests that some should have been detected, yet hitherto none has been seen. Many decades of asteroid and comet characterization have yielded formation models that explain the mass distribution, chemical abundances and planetary configuration of the Solar System today, but there has been no way of telling whether the Solar System is typical of planetary systems. Here we report observations and analysis of the object 1I/2017 U1 ('Oumuamua) that demonstrate its extrasolar trajectory, and that thus enable comparisons to be made between material from another planetary system and from our own. Our observations during the brief visit by the object to the inner Solar System reveal it to be asteroidal, with no hint of cometary activity despite an approach within 0.25 astronomical units of the Sun. Spectroscopic measurements show that the surface of the object is spectrally red, consistent with comets or organic-rich asteroids that reside within the Solar System. Light-curve observations indicate that the object has an extremely oblong shape, with a length about ten times its width, and a mean radius of about 102 metres assuming an albedo of 0.04. No known objects in the Solar System have such extreme dimensions. The presence of 'Oumuamua in the Solar System suggests that previous estimates of the number density of interstellar objects, based on the assumption that all such objects were cometary, were pessimistically low. Planned upgrades to contemporary asteroid survey instruments and improved data processing techniques are likely to result in the detection of more interstellar objects in the coming years.

Pembrolizumab Induced Acute Kidney Injury and Liver Injury in a Patient with Malignant Melanoma.

Immune checkpoint inhibitors (ICIs) have recently gained recognition as valuable treatment options for a variety of cancers. Pembrolizumab is a monoclonal antibody that acts as an inhibitor of programmed cell death receptor-1 (PD-1). This helps release host T-cells from regulatory inhibition by tumor neoantigens, therefore mediating antitumor effects. Pembrolizumab has been approved for a variety of cancers including melanoma, head and neck squamous cell carcinoma, non-small cell lung cancer, and urothelial cell carcinoma. It has also recently gained attention for possible use in hepatocellular carcinoma and triple negative breast cancer. Although efficacious, ICIs manifest a unique set of immune-related adverse effects (irAEs) including acute kidney injury (AKI) and acute liver injury (ALI) of which the mechanism is poorly understood. While these irAEs have been described previously in literature individually, there is a paucity of literature describing their simultaneous occurence. With the growing incorporation of ICIs in oncological regimens, it is important to characterize the presentation of irAEs to facilitate earlier recognition and intervention to avoid further complications. We present a case of a 60-year-old male who presented with concurrent AKI and ALI secondary to pembrolizumab therapy for advanced metastatic melanoma. To the authors' knowledge, this is the first reported incident in literature of AKI and ALI occurring simultaneously secondary to ICI immunotherapy with pembrolizumab, although each have been reported and characterized individually.

Radiation Therapy Induced Esophageal Ulcer.

Dysproteinemia is excessive production of immunoglobulins from clonal proliferation of plasma or B cells. Cryoglobulins are a special group of immunoglobulins that precipitate below 37 degrees C. Type 1 cryoglobulinemia consists mostly of IgM and IgG that infrequently leads to glomerulonephritis. In these situations, an underlying malignancy is even rare with only 21 cases described so far with only four having chronic lymphocytic leukemia (CLL). We present a case of a 68-year-old male admitted with hypertension and kidney dysfunction who upon work up was found to have CLL. Kidney biopsy was performed that showed capillary loops thickening with massive intraluminal cryoglobulin deposition in the glomeruli on periodic acid-Schiff (PAS) stain and "tram tracking" on silver stains. The patient was started on chemotherapy with rituximab, cyclophosphamide, vincristine, and prednisone. After his fourth and final cycle of treatment, the patient's serum creatinine and Glomerular filtration rate improved to 1.2 mg/dL and 85 mL/min from 3 mg/dL and 29 mL/min respectively. One month later, his renal function remained mostly unchanged. The rare association of type 1 cryoglobulinemia with underlying CLL makes it a unique and intriguing case.

Light echoes from ancient supernovae in the Large Magellanic Cloud.

The light from historical supernovae could in principle still be visible as scattered-light echoes centuries after the explosion. The detection of light echoes could allow us to pinpoint the supernova event both in position and age and, most importantly, permit the acquisition of spectra to determine the 'type' of the supernova centuries after the direct light from the explosion first reached Earth. Although echoes have been discovered around some nearby extragalactic supernovae, targeted searches have not found any echoes in the regions of historical Galactic supernovae. Here we report three faint variable-surface-brightness complexes with high apparent proper motions pointing back to three of the six smallest (and probably youngest) previously catalogued supernova remnants in the Large Magellanic Cloud, which are believed to have been thermonuclear (type Ia) supernovae. Using the distance and apparent proper motions of these echo arcs, we estimate ages of 610 and 410 years for two of them.

Ultrasound-guided Placement of a Foley Catheter Using a Hydrophilic Guide Wire.

Acute urinary retention is a common problem in the emergency department. Patients can present in significant distress, necessitating the placement of a urinary catheter. Foley catheter placement can be difficult to accomplish depending on the etiology of the retention and the degree of the obstruction. In the case presented here, we used ultrasound guidance, a guidewire, and a Foley catheter to successfully relieve a patient's urinary retention after multiple failed attempts.

Design of a nonviral vector for site-selective, efficient integration into the human genome.

Gene therapy in eukaryotes has met many obstacles. Research into the design of suitable nonviral vectors has been slow. To our knowledge, no nonviral vector has been proposed that allows for the possibility of highly efficient, site-selective integration into the genome of mammalian cells. On the basis of prior studies investigating the components necessary for transposon, retrovirus-like retrotransposon, and retroviral integration, we propose a nonviral system that would potentially allow for site-selective, efficient integration into the mammalian genome. Transposons have been developed that can transform a variety of cell lines. For example, the Sleeping Beauty transposon (SB) can transform a wide range of vertebrate cells from fish to human, and it mediates stable integration and long-term transgene expression in mice. However, the efficiency of transposition varies significantly among cell lines, suggesting the possible involvement of host factors in SB transposition. Here, we propose the use of a chimeric transposase (i.e., transposase-host DNA binding domain) to bypass the potential requirement of a host DNA-directing factor (or factors) for efficient, site-selective integration. We also discuss another potential method of docking the transposon-based vector adjacent to the host DNA, utilizing repetitive sequences for homologous recombination to promote efficient site-selective integration, as well as other site-selective nonviral approaches.

Force distributions in a triangular lattice of rigid bars.

We study the uniformly weighted ensemble of force balanced configurations on a triangular network of nontensile contact forces. For periodic boundary conditions corresponding to isotropic compressive stress, we find that the probability distribution for single-contact forces decays faster than exponentially. This superexponential decay persists in lattices diluted to the rigidity percolation threshold. On the other hand, for anisotropic imposed stresses, a broader tail emerges in the force distribution, becoming a pure exponential in the limit of infinite lattice size and infinitely strong anisotropy.

Immunotherapy and prostate cancer.

Prostate cancer is the second leading cause of cancer death in the US, largely because of the limitations of our current therapeutic options, especially once the cancer has metastasized. Investigators have long sought new therapeutic modalities such as angiogenesis inhibitors, vaccines, and gene therapy, among others. It appears that a combination approach will be required to cure the majority of malignancies. Immunotherapy for prostate cancer appears feasible and a likely therapeutic modality in the armamentarium. Unfortunately, further research in basic immunology and the interaction of the immune system with other forms of therapy is needed. Many obstacles exist in immunotherapy, including vector design, tumouricidal specificity, and tumor evasion, which will have to be overcome in order to realize the maximum therapeutic benefit from this treatment modality.

Is the routine recording of primary care consultations possible and desirable? Lessons for researchers from a consultation with multiple stakeholders.

OBJECTIVE: To explore stakeholders' attitudes towards routine, longitudinal recording of primary care consultations for research purposes, and to identify legal, ethical, and practical barriers and facilitators. METHODS: 183 stakeholders (including patients, researchers and practice staff) were identified using a purposeful sampling strategy. Stakeholders participated in focus groups and interviews. The data was analysed thematically in an iterative manner with themes and questions from earlier discussions being raised with later participants. RESULTS: Most participants supported the creation of a database and believed it would benefit patient care. They suggested it could be used to train doctors, aid understanding of conditions, and feed information back to practices to improve performance. However, enthusiasm was tempered by concerns about the ownership security and access of the data; quality and limitations of the dataset; impact on behaviour; and workload. Safeguards were suggested that protected vulnerable individuals, enabled participation, gave control to participants, and clarified data use. CONCLUSION: The findings show that collecting such longitudinal data is possible, valuable and acceptable providing certain safeguards are in place. PRACTICE IMPLICATIONS: Future studies employing routine recordings of consultations should: Attend to confidentiality, access and governance of the archive. Collect quality data, and store it securely.

The ancestral distance test: what relatedness can reveal about correlated evolution in large lineages with missing character data and incomplete phylogenies.

The ancestral distance test is introduced to detect correlated evolution between two binary traits in large phylogenies that may lack resolved subclades, branch lengths, and/or comparative data. We define the ancestral distance as the time separating a randomly sampled taxon from its most recent ancestor (MRA) with extant descendants that have an independent trait. The sampled taxon either has (target sample) or lacks (nontarget sample) a dependent trait. Modeled as a Markov process, we show that the distribution of ancestral distances for the target sample is identical to that of the nontarget sample when characters are uncorrelated, whereas ancestral distances are smaller on average for the target sample when characters are correlated. Simulations suggest that the ancestral distance can be estimated using the time, total branch length, taxonomic rank, or number of speciation events between a sampled taxon and the MRA. These results are shown to be robust to deviations from Markov assumptions. A Monte Carlo technique estimates P-values when fully resolved phylogenies with branch lengths are available, and we evaluate the Monte Carlo approach using a data set with known correlation. Measures of relatedness were found to provide a robust means to test hypotheses of correlated character evolution.

Monte Carlo algorithms for Hardy-Weinberg proportions.

The Hardy-Weinberg law is among the most important principles in the study of biological systems. Given its importance, many tests have been devised to determine whether a finite population follows Hardy-Weinberg proportions. Because asymptotic tests can fail, Guo and Thompson developed an exact test; unfortunately, the Monte Carlo method they proposed to evaluate their test has a running time that grows linearly in the size of the population N. Here, we propose a new algorithm whose expected running time is linear in the size of the table produced, and completely independent of N. In practice, this new algorithm can be considerably faster than the original method.