Unusual Near-Horizon Cosmic-Ray-like Events Observed by ANITA-IV.

ANITA's fourth long-duration balloon flight in 2016 detected 29 cosmic-ray (CR)-like events on a background of 0.37_{-0.17}^{+0.27} anthropogenic events. CRs are mainly seen in reflection off the Antarctic ice sheets, creating a phase-inverted waveform polarity. However, four of the below-horizon CR-like events show anomalous noninverted polarity, a p=5.3×10^{-4} chance if due to background. All anomalous events are from locations near the horizon; ANITA-IV observed no steeply upcoming anomalous events similar to the two such events seen in prior flights.

The effects of display size on performance.

We examined the systematic effects of display size on task performance as derived from a standard perceptual and cognitive test battery. Specifically, three experiments examined the influence of varying viewing conditions on response speed, response accuracy and subjective workload at four differing screen sizes under three different levels of time pressure. Results indicated a ubiquitous effect for time pressure on all facets of response while display size effects were contingent upon the nature of the viewing condition. Thus, performance decrement and workload elevation were evident only with the smallest display size under the two most restrictive levels of time pressure. This outcome generates a lower boundary threshold for display screen size for this order of task demand. Extrapolations to the design and implementation of all display sizes and forms of cognitive and psychomotor demand are considered.

Glucocorticoid-induced hyperglycemia is prevalent and unpredictable for patients undergoing cancer therapy: an observational cohort study.

BACKGROUND: Patients with cancer are often treated with glucocorticoids (gcs) as part of therapy, which may cause hyperglycemia. We sought to define the prevalence of, and risk factors for, hyperglycemia in this setting. METHODS: Adult patients taking gc as part of therapy protocols for primary brain tumour or metastasis, for lymphoma, or for bone marrow transplant (bmt) were screened with random glucometer measurements taken at least 3 hours after the last dose gcs. RESULTS: We screened 90 patients [44.4% women, 55.6% men; mean age: 59.6 years (range: 25-82 years); mean body mass index (bmi): 26.4 kg/m(2) (range: 15.8-45.3 kg/m(2))] receiving gc as part of cancer treatment. Mean total daily gc dose in the group was 238.5 mg (range: 30-1067 mg) hydrocortisone equivalents. Hyperglycemia (glucose ≥ 8.0 mmol/L) was found in 58.9% (53 of 90), and diabetes mellitus (dm)-range hyperglycemia (glucose ≥ 11.1 mmol/L) in 18.9% (17 of 90). The mean time from gc ingestion to glucometer testing was 5.5 hours (range: 3-20 hours). Presence of hyperglycemia did not correlate with traditional dm risk factors such as age, sex, bmi, and personal or family history of dm. A longer interval from gc dose to testing (p < 0.05), a higher gc dose (p = 0.04), and a shorter interval between the preceding meal and testing (p = 0.02) were risk factors for hyperglycemia in some patient groups. CONCLUSIONS: Glucocorticoid-induced hyperglycemia is common in patients undergoing cancer treatment and cannot be predicted by traditional risk factors for dm. We recommend that all cancer patients receiving gc be screened for hyperglycemia at least 4-6 hours after gc administration.

Transforming growth factor beta abrogates the effects of hematopoietins on eosinophils and induces their apoptosis.

Hematopoietins, interleukin (IL)-3, IL-5, and granulocyte/macrophage colony-stimulating factor (GM-CSF) have previously been shown to prolong eosinophil survival and abrogate apoptosis. The objective of this study was to investigate the effect of transforming growth factor beta (TGF-beta) on eosinophil survival and apoptosis. Eosinophils from peripheral blood of mildly eosinophilic donors were isolated to > 97% purity using discontinuous Percoll density gradient. Eosinophils were cultured with hematopoietins with or without TGF-beta for 4 d and their viability was assessed. We confirmed previous observations that hematopoietins prolonged eosinophil survival and inhibited apoptosis. TGF-beta at concentrations > or = 10(-12) M abrogated the survival-prolonging effects of hematopoietins in a dose-dependent manner and induced apoptosis as determined by DNA fragmentation in agarose gels. The effect of TGF-beta was blocked by an anti-TGF-beta antibody. The anti-TGF-beta antibody also prolonged eosinophil survival on its own. The culture of eosinophils with IL-3 and GM-CSF stimulated the synthesis of GM-CSF and IL-5, respectively, suggesting an autocrine mechanism of growth factor production. TGF-beta inhibited the synthesis of GM-CSF and IL-5 by eosinophils. TGF-beta did not have any effect on the expression of GM-CSF receptors on eosinophils. We also studied the effect of TGF-beta on eosinophil function and found that TGF-beta inhibited the release of eosinophil peroxidase. Thus, TGF-beta seems to inhibit eosinophil survival and function. The inhibition of endogenous synthesis of hematopoietins may be one mechanism by which TGF-beta blocks eosinophil survival and induces apoptosis.

Lyn, Jak2, and Raf-1 kinases are critical for the antiapoptotic effect of interleukin 5, whereas only Raf-1 kinase is essential for eosinophil activation and degranulation.

Interleukin (IL)-5 has been shown to activate many signaling molecules in eosinophils, but their functional relevance remains unknown. We have examined the functional relevance of Lyn, Jak2, and Raf-1 kinases in eosinophil survival, upregulation of adhesion molecules and degranulation. To this goal we used Lyn and Raf-1 antisense (AS) oligodeoxynucleotides (ODN) to inhibit the expression of these proteins and tyrphostin AG490 to specifically block the activation of Jak2. We have demonstrated that all three kinases are important for IL-5- induced suppression of eosinophil apoptosis. However, Lyn and Jak2 tyrosine kinases are not important for the upregulation of CD11b and the secretion of eosinophil cationic protein. In contrast, Raf-1 kinase is critical for both these functions. This is the first identification of specific signaling molecules responsible for three important functions of eosinophils. We have established a central role for Raf-1 kinase in regulating eosinophil survival, expression of beta2 integrins and degranulation. Further, there appears to be a dissociation between two receptor-associated tyrosine kinases, i.e., Lyn and Jak2, and the activation of Raf-1 kinase. The delineation of the functional relevance of signaling molecules will help design therapeutic approaches targeting specific eosinophil function.

Macrophage inflammatory protein-1 alpha activates basophils and mast cells.

Macrophage inflammatory protein-1 (MIP) is a recently cloned cytokine that causes neutrophilic infiltration and induces an inflammatory response. We studied the effect of MIP-1 alpha on histamine secretion from basophils and mast cells. Leukocytes from allergic and normal subjects were studied. MIP-1 alpha caused dose-dependent release of histamine from basophils of 14 of 20 allergic donors at concentrations of 10(-9)-10(-7) M, and the mean release was 13.50 +/- 2.9% at the highest concentration. In the same experiments, the mean histamine release by anti-immunoglobulin E and monocyte chemotactic and activating factor (MCAF) (10(-7) M) was 32 +/- 7% and 31 +/- 3%, respectively. The cells from only 2 of 10 normal subjects released histamine in response to MIP-1 alpha. Histamine release by MIP-1 alpha was rapid, and almost complete within the first 3 min. MIP-1 alpha-induced degranulation was a calcium-dependent noncytotoxic process. MIP-1 alpha showed chemotactic activity for purified basophils that was comparable to MCAF. Both MIP-1 alpha and MCAF at 10(-7) M concentration elicited a chemotactic response that was 40% of the maximal response to C5a (1 microgram/ml). Murine MIP-1 alpha induced histamine release from mouse peritoneal mast cells in a dose-dependent manner. Thus, we have established that MIP-1 alpha is a novel activator of basophils and mast cells.

Nature of packs used in propellant modeling.

In recent years we have constructed closely packed spheres using the Lubachevsky-Stillinger algorithm to generate morphological models of heterogeneous solid propellants. Improvements to the algorithm now allow us to create large polydisperse packs on a laptop computer, and to create monodisperse packs with packing fractions greater than 70% which display significant crystal order. The use of these models in the physical context motivates efforts to examine in some detail the nature of the packs, including certain statistical properties. We compare packing fractions for binary packs with long-known experimental data. Also, we discuss the near-neighbor number and the radial distribution function (RDF) for monodisperse packs and make comparisons with experimental data. We also briefly discuss the RDF for bidisperse packs. We also consider bounded monodisperse packs, and pay particular attention to the near-wall structure where we identify significant order.

Protein Cysteinyl-S-Nitrosylation: Analysis and Quantification.

The thiol moiety of cysteine residues can undergo a number of biologic modifications including oxidation, sulfenylation, nitrosylation, persulfidation, metalation, and other modifications. These modifications can control biological function, including gain as well as loss of function. Herein, we focus attention on the proteomic analysis of S-nitrosylation in health and disease. We describe a novel quantitative approach that combines accurate, sensitive fluorescence modification of cysteinyl-S-nitrosylation that leaves electrophoretic mobility unaffected (SNOFlo), and introduce unique concepts for measuring changes in S-nitrosylation status relative to protein abundance. We present several studies where suitability of this approach for investigating endogenous S-nitrosylation is addressed.

Thoracoscopic lobectomy after induction therapy-a paradigm shift?

Video-assisted thoracoscopic approaches (or VATS) have gained significant momentum in the management of locally advanced NSCLC in the current era. Accrual of experiences and concurrent improvements in instrumentation and video technology have further enhanced its role in patients with stage IIIA (N2) non-small cell lung cancer (NSCLC). However, substantial controversy exists around the notion of mediastinal staging and restaging after induction therapy, the utility of induction chemotherapy versus chemoradiation for N2 disease, and subsequent role of video-assisted thoracoscopic surgery (VATS) lobectomy following induction therapy. This perspective will closely examine these issues in the context of existing guidelines and contemporary studies.

Uniportal lobectomy and segmentectomy-is it for all?

Technological advances have markedly transformed the philosophy of thoracic surgery in the current era, with notable improvements in patient outcomes with video-assisted thoracoscopic surgery (VATS). More recently, innovations in uniportal VATS approaches have been promising, although robust data on their efficacy is limited. Nonetheless, the lessons learned from experience with the 2-port and 3-port VATS lobectomy and segmentectomy can be applied to further improve the efficacy of uniportal approaches, in terms of achieving oncologic efficacy and improving patient outcomes. This perspective reviews contemporary outcomes of uniportal lobectomy and segmentectomy, highlights our institutional experience, and examines future directions and challenges pertaining to widespread adoption of this innovative technique.

Sympathetic genital responses induced by p-chloroamphetamine in anaesthetized female rats.

In urethane-anesthetized female rats, a branch of the hypogastric nerve equivalent to the vas deferens nerve in males was shown anatomically and electrophysiologically to supply the uterine horns and we have consequently termed this the uterine nerve. Administration of p-chloroamphetamine i.v. elicited patterned bursting uterine nerve activity responses together with contractions of the uterine horns and musculature of the vaginal wall. These responses are qualitatively similar to ejaculatory responses observed following p-chloroamphetamine administration to anesthetized male rats and the urethrogenital reflex in females, suggesting they represent responses occurring during sexual processes. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8. These data indicate that common neurophysiological and pharmacological mechanisms regulate genital reflexes at the lumbosacral spinal level in both the female and the male rat.

Activation by p-chloroamphetamine of the spinal ejaculatory pattern generator in anaesthetized male rats.

In urethane-anesthetized male rats, a branch of the hypogastric nerve was shown, anatomically and electrophysiologically, to supply the vas deferens. Recordings from this nerve revealed a low level of tonic activity, which was predominantly efferent motor activity. Administration of p-chloroamphetamine i.v., elicited a rhythmic burst of neuronal activity, coherent with rhythmic pressure increases in the vas deferens and contractions of the bulbospongiosus muscles, which together comprise ejaculation. This response to p-chloroamphetamine was still present after complete transection of the spinal cord at T8-T9. These data indicate that p-chloroamphetamine is capable of activating the spinal neuronal circuits that generate the pattern of autonomic and somatic responses similar to those of sexual climax. Furthermore based on the best documented action of p-chloroamphetamine, the results suggest that the excitability of the pattern generator is regulated by serotonergic, dopaminergic or noradrenergic receptors in the lumbosacral spinal cord. We conclude this animal model will enable robust studies of the pharmacology and physiology of central neural mechanisms involved in ejaculation and sexual climax.

Activation of D2-like receptors induces sympathetic climactic-like responses in male and female anaesthetised rats.

In anaesthetised male rats an intravenous (i.v.) injection of p-chloroamphetamine (PCA) produced a specific patterned bursting response in the sympathetic vas deferens nerve (VDN) that corresponds to ejaculation. In the present, study selective dopamine agonists and antagonists were used to investigate whether dopaminergic mechanisms influence the generation of this ejaculatory-related response. Administration of a mixed D(1/2) receptor agonist (0.1-1.0 mg kg(-1) apomorphine i.v.) also evoked the characteristic bursting pattern responses in the VDN. Similar, but fewer, burst pattern responses could also be evoked by a selective D(2/3) receptor agonist (0.1-2.0 mg kg(-1) piribedil). Responses to 1.0 mg kg(-1) apomorphine were blocked by pretreatments with either 0.5 mg kg(-1) remoxipride (D(2) receptor antagonist) or 0.5 mg kg(-1) nafadotride (D(3) receptor antagonist), suggesting that D(2)-like receptors were involved. Responses could not be evoked by i.v. injections of apomorphine (1.0 mg kg(-1)) in anaesthetised male rats with a midthoracic spinal section, indicating that activation of D(2)-like receptors at supraspinal sites leads to an increase in the excitability of the lumbosacral pattern generator for ejaculation. In anaesthetised female rats a similar patterned bursting response occurred in the uterine nerve (UN) in response to apomorphine (0.5-2.0 mg kg(-1) i.v.). Thus a common neural mechanism may regulate sexual climactic reflexes in both sexes.

An isolated case of leprosy presenting in a migrant worker in Northern Ireland.

Leprosy was first recorded in 600 bc in India. Europe saw its first cases in the fourteenth century. The worldwide incidence is falling, but the disease can still present in the most unexpected places: this is a report of the first case of leprosy presenting to an emergency department in Northern Ireland. It is important for physicians in both community and hospital medicine to have a high index of suspicion for leprosy in patients with chronic skin conditions who were born outside the UK or other developed countries.

Modified uniportal video-assisted thoracoscopic surgery (VATS).

Video-assisted thoracoscopic surgery (VATS) for resectable lung cancer patients has been frequently used in the past decades. The potential beneficial advantages and safety of VATS has been shown in large patient series and meta-analyses. The strategy of limiting access to one incision in one intercostal space (uniportal VATS) has been adopted by some thoracic surgeons in recent years. We have described a modified uniportal VATS technique with its potential advantages. Modified uniportal VATS potentially offers better exposure, beneficial opportunities for education and improved comfort for the thoracic surgery team in clinical usage.

Troubleshooting hilar and interlobar lymphadenopathy during thoracoscopic lobectomy for benign disease-case report.

The completion of thoracoscopic lobectomy can be more difficult in the setting of clinically positive lymph nodes, which may be found in the setting of a proximal tumor causing bronchial obstruction or a larger tumor which may create an inflammatory state, both of which cause benign significant enlargement of hilar lymph nodes. Knowledge of the typical locations of these enlarged nodes facilitates the conduct of the operation. For all video-assisted thoracoscopic surgery (VATS) lobectomies, it is prudent to remove all visible lymph nodes prior to arterial and bronchial dissection. Moreover, in cases of significant hilar adenopathy, this strategy becomes more important and effective. For left upper lobectomy, the removal of level 11 lymph node anteriorly improves visualization of both bronchi, the interlobar pulmonary artery, the arterial aspect of the fissure, and the lingular artery. Subsequent dissection of the level 10 lymph node superior to the upper lobe bronchus exposes the main pulmonary artery and the truncal branches. For right upper lobectomy, dissection of the level 11 lymph node posteriorly not only exposes the upper lobe bronchus, but also the adjacent posterior ascending pulmonary artery. Dissection of the level 10 lymph node at the superior hilum facilitates exposure of the right pulmonary artery.

Division of the bronchus: an approach to the intraoperative management of difficult lymphadenopathy.

BACKGROUND: A minimally invasive approach to lung cancer resection offers many benefits over traditional open surgery. Reasons for increased difficulty and conversion from thoracoscopic to open surgery have been studied and include abnormal hilar or interlobar lymphadenopathy. METHODS: We present a case of adherent lymphadenopathy complicating dissection of the truncus anterior branch of the pulmonary artery during thoracoscopic left upper lobectomy. RESULTS: We show one approach to the management of difficult lymphadenopathy and pulmonary arterial isolation, that of division without closure of the lobar bronchus to allow superior access to the branches of the pulmonary artery, followed by stapled closure of the bronchus. CONCLUSIONS: While adherent lymphadenopathy is a vexing problem in thoracoscopic lobectomy, minimallyinvasive approaches are safe and effective. We show that division of the bronchus can improve exposure and allow safe dissection to proceed.

Management of pulmonary arterial bleeding in the post induction setting.

BACKGROUND: A minimally invasive approach to lung cancer resection offers many benefits over traditional open surgery. Pulmonary arterial injury is a widely cited reason for conversion to open surgery. METHODS: We present a case of pulmonary arterial injury complicating dissection of the pulmonary artery during thoracoscopic left upper lobectomy. Ethical approval was obtained from the institutional ethics board and written consent was obtained from the patient. RESULTS: Thoracoscopic management of pulmonary arterial bleeding is demonstrated. We show maintenance of a thoracoscopic approach with establishment of proximal pulmonary arterial control, allowing suture repair of an injury to the ongoing pulmonary artery. CONCLUSIONS: While pulmonary arterial injury may be a significant problem during thoracoscopic lobectomy, minimally invasive approaches to repair are safe and effective.

Long-term treatment with the dipeptidyl peptidase IV inhibitor P32/98 causes sustained improvements in glucose tolerance, insulin sensitivity, hyperinsulinemia, and beta-cell glucose responsiveness in VDF (fa/fa) Zucker rats.

The incretins, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) are responsible for >50% of nutrient-stimulated insulin secretion. After being released into the circulation, GIP and GLP-1 are rapidly inactivated by the circulating enzyme dipeptidyl peptidase IV (DP IV). The use of DP IV inhibitors to enhance these insulinotropic hormonal axes has proven effective on an acute scale in both animals and humans; however, the long-term effects of these compounds have yet to be determined. Therefore, we carried out the following study: two groups of fa/fa Zucker rats (n = 6 each) were treated twice daily for 3 months with the DP IV inhibitor P32/98 (20 mg.kg(-1).day(-1), p.o.). Monthly oral glucose tolerance tests (OGTTs), performed after drug washout, revealed a progressive and sustained improvement in glucose tolerance in the treated animals. After 12 weeks of treatment, peak OGTT blood glucose values in the treated animals averaged 8.5 mmol/l less than in the controls (12.0 +/- 0.7 vs. 20.5 +/- 1.3 mmol/l, respectively). Concomitant insulin determinations showed an increased early-phase insulin response in the treated group (43% increase). Furthermore, in response to an 8.8 mmol/l glucose perfusion, pancreata from controls showed no increase in insulin secretion, whereas pancreata from treated animals exhibited a 3.2-fold rise in insulin secretion, indicating enhanced beta-cell glucose responsiveness. Also, both basal and insulin-stimulated glucose uptake were increased in soleus muscle strips from the treated group (by 20 and 50%, respectively), providing direct evidence for an improvement in peripheral insulin sensitivity. In summary, long-term DP IV inhibitor treatment was shown to cause sustained improvements in glucose tolerance, insulinemia, beta-cell glucose responsiveness, and peripheral insulin sensitivity, novel effects that provide further support for the use of DP IV inhibitors in the treatment of diabetes.

Training Assistants Improves the Process of Adoption of Video-Assisted Thoracic Surgery Lobectomy.

BACKGROUND: Despite overwhelming evidence of decreased pain, fewer complications, and shorter length of stay with equivalent oncologic outcomes, video-assisted thoracic surgery (VATS) lobectomy has been slow to be adopted in the community. This study evaluates the role of training surgical assistants to ease the transition to VATS lobectomy. METHODS: A half-day training course for physician assistants in the specific skills needed to assist with VATS lobectomy was developed to be offered annually in conjunction with a national meeting. Each participant completed a needs assessment before the course and a course assessment afterward. One-year follow-up data were obtained from the first cohort to determine the effects of the course on their practice. RESULTS: Forty-four physician assistants participated in the course in either 2013 or 2014. Participant-identified educational needs included enhanced camera navigation skills, use of specialized instruments, and knowledge of the steps of the operation to provide proactive assistance. After completing the course, 90% (n = 39) felt more confident in their ability to provide optimal visualization for the operating surgeon, and 93% (n = 40) felt more confident in their ability to recognize and anticipate the steps of a VATS lobectomy. These changes persisted at 1 year. CONCLUSIONS: Specific training directed at surgical assistants may improve the adoption of new technology by mechanisms including improved visualization and better understanding of methods to facilitate the operation and avoid frustration. This type of training should be made available to assistants of surgeons learning new operations.