Intense chorus waves are the cause of flux-limiting in the heart of the outer radiation belt.

Chorus waves play a key role in outer Van Allen electron belt dynamics through cyclotron resonance. Here, we use Van Allen Probes data to reveal a new and distinct population of intense chorus waves excited in the heart of the radiation belt during the main phase of geomagnetic storms. The power of the waves is typically ~ 2-3 orders of magnitude greater than pre-storm levels, and are generated when fluxes of ~ 10-100 keV electrons approach or exceed the Kennel-Petschek limit. These intense chorus waves rapidly scatter electrons into the loss cone, capping the electron flux to a value close to the limit predicted by Kennel and Petschek over 50 years ago. Our results are crucial for understanding the limits to radiation belt fluxes, with accurate models likely requiring the inclusion of this chorus wave-driven flux-limiting process, that is independent of the acceleration mechanism or source responsible for enhancing the flux.

Resolving Magnetopause Shadowing Using Multimission Measurements of Phase Space Density.

Loss mechanisms act independently or in unison to drive rapid loss of electrons in the radiation belts. Electrons may be lost by precipitation into the Earth's atmosphere, or through the magnetopause into interplanetary space-a process known as magnetopause shadowing. While magnetopause shadowing is known to produce dropouts in electron flux, it is unclear if shadowing continues to remove particles in tandem with electron acceleration processes, limiting the overall flux increase. We investigated the contribution of shadowing to overall radiation belt fluxes throughout a geomagnetic storm starting on the 7 September 2017. We use new, multimission phase space density calculations to decipher electron dynamics during each storm phase and identify features of magnetopause shadowing during both the net-loss and the net-acceleration storm phases on sub-hour time scales. We also highlight two distinct types of shadowing; "direct," where electrons are lost as their orbit intersects the magnetopause, and "indirect," where electrons are lost through ULF wave driven radial transport toward the magnetopause boundary.

STELA (Smart TV and smartphone-basEd Laparoscopy TrAiner): a no-cost home-based trainer for beginners.

BACKGROUND: Proficiency in laparoscopy is gradually achieved. After initial simulation, it is safe to move to real patients. Simulation improves the basic attributes of laparoscopy, and its non-availability hampers training. Virtual reality and commercial simulators are exorbitantly expensive. Cheaper non-commercial latest, mobile phone-based simulators appear ergonomically unsuitable. A need for a no-cost, home-based laparoscopic endotrainer was felt by authors. METHODS: The authors proposed the concept of smart TV and smart phone-based laparoscopy trainer (STELA), an almost zero cost, lightweight indigenous, cable-less box-type endotrainer, with a smart phone housed on the model, projecting to smart TV via Wi-fi direct. The simulation timings on STELA were compared with Universal Beetel endotrainer by a group of surgeons and residents using identical tasks like object transfer (OT) and knot making (KM). RESULTS: Data were analysed using SPSS, version 23.There was no significant difference in the mean timings of the residents (p > 0.05) on two endotrainers, for both tasks, and of surgeons for OT. Surgeons took significantly longer time (p < 0.05) in KM on STELA. Highest correlation (r = +.848) (<.05) was seen for KM on both devices by residents. CONCLUSION: STELA is a viable, technologically advanced, no cost alternative to the non-commercial cumbersome simulators especially for beginners.

Severe acute respiratory syndrome coronavirus 2 may be an underappreciated pathogen of the central nervous system.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a highly contagious respiratory disease referred to as COVID-19. However, emerging evidence indicates that a small but growing number of COVID-19 patients also manifest neurological symptoms, suggesting that SARS-CoV-2 may infect the nervous system under some circumstances. SARS-CoV-2 primarily enters the body through the epithelial lining of the respiratory and gastrointestinal tracts, but under certain conditions this pleiotropic virus may also infect peripheral nerves and gain entry into the central nervous system (CNS). The brain is shielded by various anatomical and physiological barriers, most notably the blood-brain barrier (BBB) which functions to prevent harmful substances, including pathogens and pro-inflammatory mediators, from entering the brain. The BBB is composed of highly specialized endothelial cells, pericytes, mast cells and astrocytes that form the neurovascular unit, which regulates BBB permeability and maintains the integrity of the CNS. In this review, potential routes of viral entry and the possible mechanisms utilized by SARS-CoV-2 to penetrate the CNS, either by disrupting the BBB or infecting the peripheral nerves and using the neuronal network to initiate neuroinflammation, are briefly discussed. Furthermore, the long-term effects of SARS-CoV-2 infection on the brain and in the progression of neurodegenerative diseases known to be associated with other human coronaviruses are considered. Although the mechanisms of SARS-CoV-2 entry into the CNS and neurovirulence are currently unknown, the potential pathways described here might pave the way for future research in this area and enable the development of better therapeutic strategies.

Tumor mutational burden is predictive of response to immune checkpoint inhibitors in MSI-high metastatic colorectal cancer.

BACKGROUND: Microsatellite instability (MSI) is a biomarker for response to immune checkpoint inhibitors (ICPIs). PD-1 inhibitors in metastatic colorectal carcinoma (mCRC) with MSI-high (MSI-H) have demonstrated a high disease control rate and favorable progression-free survival (PFS); however, reported response rates to pembrolizumab and nivolumab are variable and often <50%, suggesting that additional predictive biomarkers are needed. METHODS: Clinicopathologic data were collected from patients with MSI-H mCRC confirmed by hybrid capture-based next-generation sequencing (NGS) treated with PD-1/L1 inhibitors at five institutes. Tumor mutational burden (TMB) was determined on 0.8-1.1 Mb of sequenced DNA and reported as mutations/Mb. Potential biomarkers of response and time to progression were analyzed by univariate and multivariate analyses. Once TMB was confirmed as a predictive biomarker, a larger dataset of 18 140 unique CRC patients was analyzed to define the relevance of the identified TMB cut-point. RESULTS: A total of 22 patients were treated with PD-1/L1 inhibitors including 19 with pembrolizumab monotherapy. Among tested variables, TMB showed the strongest association with objective response (OR; P < 0.001) and PFS, by univariate (P < 0.001) and multivariate analysis (P < 0.01). Using log-rank statistics, the optimal predictive cut-point for TMB was estimated between 37 and 41 mutations/Mb. All 13 TMBhigh cases responded, while 6/9 TMBlow cases had progressive disease. The median PFS for TMBhigh has not been reached (median follow-up >18 months) while the median PFS for TMBlow was 2 months. A TMB of 37.4 mutations/Mb in a large MSI-H mCRC population (821/18, 140 cases; 4.5%) evaluated by NGS corresponded to the 35th percentile cut-point. CONCLUSIONS: TMB appears to be an important independent biomarker within MSI-H mCRC to stratify patients for likelihood of response to ICPIs. If validated in prospective studies, TMB may play an important role in guiding the sequencing and/or combinations of ICPIs in MSI-H mCRC.

Safety and efficacy of total intraluminal topical anaesthesia for ureteroscopy. Is success worth the pain?

BACKGROUND: Ureteroscopic management of ureteral calculi using topical anaesthesia has been described. Most studies topically anaesthetized the urethra or urinary bladder by instilling 2% of plain lignocaine. In addition to the success rate, the pain perception in these studies was reported subjectively using non-standard criteria. Topical anaesthesia of the ipsilateral ureter and the pelvicalyceal system (PCS), in addition to urethra and urinary bladder, and use of alkalinised lignocaine, for enhanced effect, has not been reported for ureteroscopy. Using these conceptual alterations, we tested the safety and efficacy of performing ureteroscopy and laser lithotripsy under our technique of total intraluminal topical anaesthesia (TILTA). METHODS: One hundred sixty-eight patients underwent ureteroscopic laser lithotripsy by topical instillation of alkalinised lignocaine into the urinary bladder and ipsilateral ureter and PCS. Self-assessed pain perception and changes in vital parameters were objectively scored at various times. The success rate, reasons for failure, maximum pain scores, complications, and willingness to undergo repeat procedure were recorded. RESULTS: The success rate was 91.3% with a mean duration of 14.7 minutes Double J Stent (DJS) was placed in 38.1%. 61.3% patients did not need any postoperative injectable analgesic, with 11.3% requiring more than a single dose. The intraoperative changes in vitals initially and at the height of pain were not statistically significant (p>0.05). Self-assessed median pain scores between intravenous access placement and ureteroscopy were significantly different (p<0.05). CONCLUSIONS: Ureteroscopy, effectively performed under TILTA, is safe with a high success rate. The acceptable pain tolerance and the shortened convalescence in addition makes the procedure's success worth the pain.

Effect of Hemodialysis on Corrected QT Interval and QTc Dispersion.

Hemodialysis patients are at higher risk of cardiovascular disease due to traditional and dialysis-related risk factors. Our aim was to study the effects of hemodialysis on the corrected QT interval (QTc) and QTc dispersion in chronic kidney disease (CKD) without clinically manifest heart disease. Two hundred cases of CKD on chronic intermittent hemodialysis of >3 months' duration were included in the study. Twelve-lead electrocardiography and samples for serum creatinine, potassium, calcium, and magnesium were taken before and after dialysis. The mean age of patients was 52.4 ± 17 years with male-to-female ratio of 3:1. QTc interval and QTc dispersion were prolonged in 47% and 59% before and 50% and 89% of patients after hemodialysis, respectively. The mean values of QTc were 433.4 ± 36.9 ms before and 451.4 ± 39.6 ms after hemodialysis (p = 0.001) and the mean values of QTc dispersion were 60.5 ± 19.3 ms before and 81.5 ± 24.4 ms after hemodialysis (p = 0.001). Similar pattern was observed in all etiological groups of CKD, except for QTc dispersion in malignancy-related CKD (p = 0.216). After hemodialysis, there was a significant fall in the mean values of serum potassium (p = 0.001), rise in serum calcium (p = 0.001), and no change in magnesium (p = 0.424). Patients with post hemodialysis QTc dispersion >74 ms had significantly low mean values of serum potassium and calcium as compared to <74 ms group. Large numbers of hemodialysis patients have a prolonged QTc interval and QTc dispersion with a significant increase in the mean values after hemodialysis. There is a significant fall in serum potassium and rise in serum calcium after dialysis.

Gonorrhea in Canada, 2010-2015.

BACKGROUND: Gonorrhea is the second most commonly reported sexually transmitted infection (STI) in Canada after chlamydia, and rates for this STI have been increasing since 1997. OBJECTIVE: To summarize trends observed in gonorrhea rates for 2010-2015 in Canada. METHODS: Laboratory-confirmed cases of gonorrhea are reported to the Public Health Agency of Canada (PHAC) by all of the Canadian provinces and territories. The overall national rate was computed, as were rates per sex, age group and province/territory. RESULTS: In 2015, 19,845 cases of gonorrhea were reported in Canada, corresponding to a rate of 55.4 cases per 100,000 population and a 65.4% increase from 2010 (33.5 cases per 100,000 population). Males had consistently higher rates than did females (70.2 per 100,000 versus 40.6 per 100,000 in 2015) and faster rising rates (85.2% versus 39.5% in 2010-2015). Rates among adults 60 years and older increased faster than rates among younger people, although the highest rates were among those 15-29 years of age. The Northwest Territories, Nunavut and Yukon had the highest gonorrhea rates in 2015. CONCLUSION: Males, adolescents and young adults continue to represent the majority of gonorrhea cases. Research is needed to better understand the current trends in gonorrhea infection in order to maintain, evaluate and improve primary and secondary STI prevention activities.

Infectious and congenital syphilis in Canada, 2010-2015.

BACKGROUND: Syphilis is the third most commonly reported notifiable sexually transmitted infection (STI) in Canada, following chlamydia and gonorrhea, respectively. Rates of this STI have been rising rapidly in Canada since 2001. OBJECTIVE: To summarize trends observed in syphilis rates for 2010 to 2015 in Canada. METHODS: Laboratory-confirmed cases of infectious syphilis and early congenital syphilis were reported to the Public Health Agency of Canada by all of the Canadian provinces and territories. National infectious syphilis rates were computed, as were rates per sex, age group and province/territory. Rates of congenital syphilis were also calculated. RESULTS: From 2010 to 2015, the rate of infectious syphilis in Canada increased by 85.6%, from 5.0 to 9.3 cases per 100,000 population. In 2015, a total of 3,321 cases of infectious syphilis were reported, mainly in males (93.7%), among whom the rate was 17.5 cases per 100,000 males versus 1.2 per 100,000 females. The rate also rose faster among males in 2010-2015, a 90.2% increase versus 27.8% among females. Individuals aged 20-39 years had the highest rates. Across the provinces and territories, the highest rates of infectious syphilis were in Nunavut, British Columbia and Manitoba.​: The rate of congenital syphilis decreased from 2010 to 2014 (1.6 to 0.3 cases per 100,000 live births) before increasing to 1.5 cases per 100,000 live births in 2015, which corresponds to six reported cases. CONCLUSION: Rates of syphilis continue to rise in Canada, especially among young men, and this is consistent with trends in the United States of America and European Union. Based on data from Canada and from these regions, the sexual behaviour of men who have sex with men (MSM) is thought to be a major risk factor for syphilis.

Chlamydia in Canada, 2010-2015.

BACKGROUND: Chlamydia is the most commonly reported notifiable sexually transmitted infection in Canada. Rates have been steadily increasing since 1997. OBJECTIVE: To summarize trends in chlamydia rates for the period 2010-2015 in Canada. METHODS: Laboratory-confirmed cases of chlamydia were reported to the Public Health Agency of Canada by all the Canadian provinces and territories. The overall national rate was computed, as were rates per sex, age group and province/territory. RESULTS: In 2015, a total of 116,499 cases of chlamydia were reported in Canada, corresponding to a rate of 325 cases per 100,000 population. Females accounted for the majority (two-thirds) of chlamydia infections from 2010 to 2015. However, rates among males rose faster during this time period. Youth and young adults aged 15-29 years had the highest rates in 2015. While increased rates were observed over time for most age groups, adults aged 40 years and older had the greatest increase (51%) between 2010 and 2015. Chlamydia rates increased in most provinces during this period, with the highest rates being reported by the Northwest Territories and Nunavut in 2015. CONCLUSION: Between 2010 and 2015, chlamydia rates increased by 16.7% and were highest among females and young adults. Although a number of factors may account for this rising trend, the possibility of a true increase in incidence cannot be ruled out. Ongoing monitoring of chlamydia and research into the reasons for the observed changes will help guide sexually transmitted infection (STI) prevention and control activities.

Intratympanic steroid use for idiopathic sudden sensorineural hearing loss: current otolaryngology practice in Germany and Austria.

AIMS: The frequency of the use of intratympanic steroids (ITS) as a treatment for idiopathic sudden sensorineural hearing loss (ISSNHL) in Europe is still unknown and remains a contentious issue amongst otolaryngologists. We undertook a survey of otolaryngologists in Germany and Austria to establish if there is any professional consensus with which to form a protocol for its use. METHODS: A survey of 21 questions was distributed electronically to otolaryngologists in Germany and Austria and data on demographics, indications for intratympanic treatment, procedure, follow-up, and outcomes were analysed. RESULTS: We received 908 responses. 49.1% of otolaryngologists used ITS for ISSNHL. Of those otolaryngologists who use ITS, 73.7% do not use it as primary treatment. 20.6% use ITS in conjunction with oral steroids for primary treatment and only 5.8% use ITS as monotherapy for primary treatment. 90.5% use ITS as salvage therapy. 81.1% do not consider the use of ITS after 2 weeks from the onset of symptoms. 8.3% used a tympanostomy tube and while the most commonly used steroid was dexamethasone at a concentration of 4 mg/ml (61%), a wide variety or other steroids and concentrations were used. CONCLUSIONS: This survey illustrates wide variation of current practice of intratympanic corticosteroid injection for ISSHL in Germany and Austria. In the absence of high-level evidence, knowing what current practice is allows clinicians to assess what they do against what their colleagues are doing, and if they do something very different, make them question their practice. Moreover, the obtained data will help to direct future clinical trials with the aim to compare the outcomes of more commonly used protocols.

Energization of the Ring Current by Substorms.

The substorm process releases large amounts of energy into the magnetospheric system, although where the energy is transferred to and how it is partitioned remains an open question. In this study, we address whether the substorm process contributes a significant amount of energy to the ring current. The ring current is a highly variable region, and understanding the energization processes provides valuable insight into how substorm-ring current coupling may contribute to the generation of storm conditions and provide a source of energy for wave driving. In order to quantify the energy input into the ring current during the substorm process, we analyze Radiation Belt Storm Probes Ion Composition Experiment and Helium Oxygen Proton Electron ion flux measurements for H+, O+, and He+. The energy content of the ring current is estimated and binned spatially for L and magnetic local time. The results are combined with an independently derived substorm event list to perform a statistical analysis of variations in the ring current energy content with substorm phase. We show that the ring current energy is significantly higher in the expansion phase compared to the growth phase, with the energy enhancement persisting into the substorm recovery phase. The characteristics of the energy enhancement suggest the injection of energized ions from the tail plasma sheet following substorm onset. The local time variations indicate a loss of energetic H+ ions in the afternoon sector, likely due to wave-particle interactions. Overall, we find that the average energy input into the ring current is ∼9% of the previously reported energy released during substorms.

To evaluate the safety and efficacy of the TVT-Secur procedure in the treatment of stress urinary incontinence in women.

BACKGROUND: The prevalence of stress urinary incontinence (SUI) in the middle-aged Indian women is around 16%. The use of transvaginal tapes (TVTs) has revolutionised the surgical management of SUI. Patients who undergo placement of the tape via the transobturator route often complain of persistent thigh pain at the site of trocar insertion. The use of minimally invasive tapes with a single suburethral incision reduces surgical trauma by eliminating thigh incisions, while maintaining the cure achieved by conventional TVTs. The study was conducted to test the efficacy and safety of minimally invasive TVT-Secur tape placement for treatment of SUI in women. METHODS: 20 women with stress incontinence were implanted with TVT-Secur tapes and followed up for a year. RESULTS: The objective cure rate of SUI was 85% at the end of a year. The improvement in the patient satisfaction and Incontinence-specific QOL scores, of both Urogenital Distress Inventory (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7), was statistically significant at 95% and 99% confidence levels. There were no complaints of thigh pain; however, there were intraoperative complications in the form of bladder perforation in 5% (n = 1), urethral injury in 5% (n = 1) and urethral tape exposure in 10% (n = 2), at 3 months requiring tape sectioning. CONCLUSIONS: These cure rates and complications are comparable to the standard TVT implantations at the end of a year, without thigh pain; however, a greater number of patients and a longer follow-up is required to see whether the long-term cure is maintained or not, before recommending the same as a standard of treatment.

Demonstration of a near-IR line-referenced electro-optical laser frequency comb for precision radial velocity measurements in astronomy.

An important technique for discovering and characterizing planets beyond our solar system relies upon measurement of weak Doppler shifts in the spectra of host stars induced by the influence of orbiting planets. A recent advance has been the introduction of optical frequency combs as frequency references. Frequency combs produce a series of equally spaced reference frequencies and they offer extreme accuracy and spectral grasp that can potentially revolutionize exoplanet detection. Here we demonstrate a laser frequency comb using an alternate comb generation method based on electro-optical modulation, with the comb centre wavelength stabilized to a molecular or atomic reference. In contrast to mode-locked combs, the line spacing is readily resolvable using typical astronomical grating spectrographs. Built using commercial off-the-shelf components, the instrument is relatively simple and reliable. Proof of concept experiments operated at near-infrared wavelengths were carried out at the NASA Infrared Telescope Facility and the Keck-II telescope.

Shigella flexneri serotype 1 infections in men who have sex with men in Vancouver, Canada.

OBJECTIVES: Outbreaks of shigellosis have been documented in men who have sex with men (MSM), associated with interpersonal transmission and underlying HIV infection. We observed a rise in Shigella flexneri isolates identified in a downtown tertiary-care hospital laboratory located within the city centre community health area (CHA-1) of Vancouver, Canada. The objectives of this study were to evaluate clinical outcomes of shigellosis cases among MSM admitted to hospital and to evaluate trends in Shigella cases within Vancouver, Canada. METHODS: Adult rates of shigellosis were analysed by gender and health region, from 2005 to 2011, followed by retrospective chart review of all hospital laboratory-identified S. flexneri cases from 2008 to 2012. Serotyping and pulsed-field gel electrophoresis (PFGE) were performed on these isolates. RESULTS: Although shigellosis rates in men within CHA-1 did not change from 2005 to 2011 (range 33.4-68.5 per 100 000; P = 0.74), they were significantly higher than in other regions within the city of Vancouver (P ≤ 0.001) and the province of British Columbia (P ≤ 0.001). Shigella flexneri rates in men within CHA-1 increased significantly (range 2.3-51.4 per 100 000; P < 0.001), starting in 2008, and were higher than in other regions within Vancouver (P ≤ 0.01). Seventy-nine isolates of S. flexneri from 72 patients were identified by a single hospital laboratory. All patients were male and predominantly MSM (91.7%) and HIV-infected (86.1%), with most (92.6%) demonstrating CD4 counts ≥ 200 cells/µL. In total, 38.0% required hospitalization. Most (87.3%) had S. flexneri serotype 1 infection, with 72.9% of these representing a single PFGE pattern. CONCLUSIONS: We identified high levels of transmission of a primarily clonal strain of S. flexneri serotype 1 in our local MSM population, resulting in a substantial burden of illness and health care resource use secondary to hospital admissions.

Falling off the bandwagon? Exploring the challenges to sustained digital engagement by older people.

OBJECTIVES: This study examines older people's use of information and communication technologies (ICTs) and identifies the factors which can prevent or promote their sustained use. METHODS: A mixed methods approach was adopted. Quantitative and qualitative data were collected by a survey of 323 older ICT users (aged ≥50 years) between 2011 and 2012. These data were supplemented by qualitative data obtained through in-depth interviews, focus groups and storytelling. Quantitative data were analysed using PASW including bivariate and multivariate analyses. Qualitative data were analysed using an inductive, thematic approach. RESULTS: The findings show that, contrary to some stereotypes, many older people are enthusiastic, competent and confident users of ICTs. However, they report a range of challenges in reaching and maintaining this situation. These include technological complexity and change, age-related capability changes and a lack of learning and support mechanisms. Intrinsic motivation and social support are important in enabling older people to overcome these challenges. DISCUSSION: Getting older people online has been a high priority in many countries over the past decade. However, little attention has been paid to whether and how their usage can be sustained over time. We discuss the implications of the findings for policy and practice.