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Numerical simulations have predicted that substructures such as spiral arms can be produced through a gravitationally unstable disk around high-mass young stellar objects (HMYSOs). Recent high-resolution observations from the Atacama Large Millimeter/submillimeter Array have investigated these substructures at a spatial resolution of ∼100 au. An accretion burst, which is a manifestation of an increase in the accretion rate caused by a gravitational instability in the disk, can result in luminosity outbursting phenomena - as has been seen in several HMYSOs. However, no clear relationship between the accretion bursts and disk substructures has been established. Here we report the detections of three new molecular maser species, HDO, HNCO and 13CH3OH, from the direction of the HMYSO G358.93-0.03 during a 6.7 GHz methanol maser flaring event. High-quality imaging of the three new maser species exhibits consistent observational evidence that these masers closely trace the spiral-arm substructures around this HMYSO. The rapid decay of the spectral lines emitted from these molecules suggests that these are transient phenomena (for only ∼1 month), probably associated with rapid changes in radiation field due to an accretion burst. Therefore, these new maser species provide evidence linking the spiral-arm substructure with an accretion burst, both expected from massive disk instabilities.

Background Multiparametric magnetic resonance imaging (mpMRI) may improve prostate cancer risk stratification and decrease the need for repeat biopsies in men on prostate cancer active surveillance (AS). However, the impact of mpMRI on AS-related healthcare spending has not been established. Objective To characterize the impact of mpMRI on AS-related Medicare expenditures. Design, setting, and participants Using Surveillance, Epidemiology, and End Results (SEER)-Medicare files, we identified men ≥66 yr old with localized prostate cancer diagnosed during 2008–2013. Outcome measures and statistical analysis With a validated algorithm, we classified men into AS with and without mpMRI groups. We then determined Medicare spending on AS in each group using inflation-adjusted, price-standardized Medicare payments for AS-related procedures (ie, prostate-specific antigen [PSA] tests, prostate biopsies, biopsy complications, and mpMRI). Multivariable median regression compared Medicare spending on AS for men who received mpMRI and those who did not. Results and limitations We identified 9081 men on AS with a median follow-up of 45 mo (interquartile range 29–64 mo). Thirteen percent (N = 1225) received mpMRI. On multivariable median regression, receipt of mpMRI was associated with an additional $447 (95% confidence interval $409–487) in Medicare spending per year. We observed greater frequency of AS-related procedures and higher spending for identical procedures (eg, PSA or prostate biopsy) in the mpMRI group than in the non-mpMRI group (all p Conclusions Among Medicare beneficiaries on AS, mpMRI is associated with additional annual Medicare spending. Future studies are needed to determine optimal use of mpMRI during AS to maximize value. Patient summary Prostate magnetic resonance imaging (MRI) helps physicians determine which prostate cancers are aggressive and which can be monitored safely. We studied whether using MRI during prostate cancer monitoring (also called active surveillance) resulted in increased healthcare spending. There was a modest increase in spending, but this may be worthwhile if the use of MRI allows physicians to monitor prostate cancer more accurately.

Generally, in film theory, when a writer tackles such mainstream or popular artists like director, writer, and producer John Hughes, the essay or book gets bogged down by complicated wording, postm...

We present the most complete to date interferometric study of the centimeter-wavelength methanol masers detected in G358.93-0.03 at the burst and post-burst epochs. A unique, near-IR/(sub)millimeter-dark and far-IR-loud massive young stellar object accretion burst was recently discovered in G358.93-0.03. The event was accompanied by flares of an unprecedented number of rare methanol maser transitions. The first images of three of the newly discovered methanol masers at 6.18, 12.23, and 20.97 GHz are presented in this work. The spatial structure evolution of the methanol masers at 6.67, 12.18, and 23.12 GHz is studied at two epochs. The maser emission in all detected transitions resides in a region of 1/40.″2 around the bursting source and shows a clear velocity gradient in the north-south direction, with redshifted features to the north and blueshifted features to the south. A drastic change in the spatial morphology of the masing region is found: a dense and compact "spiral"cluster detected at epoch I evolved into a disperse, "round"structure at epoch II. During the transition from the first epoch to the second, the region traced by masers expanded. The comparison of our results with the complementary Very Large Array, very long baseline interferometry, Submillimeter Array, and Atacama Large Millimeter/submillimeter Array maser data is conducted. The obtained methanol maser data support the hypothesis of the presence of spiral arm structures within the accretion disk, which was suggested in previous studies of the source. © 2022. The Author(s). Published by the American Astronomical Society. The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc. This paper makes use of the following ALMA data: ADS/JAO.ALMA#2018.A.00031.TS. ALMA is a partnership of ESO (representing its member states), NSF (USA) and NINS (Japan), together with NRC (Canada), MOST and ASIAA (Taiwan), and KASI (Republic of Korea), in cooperation with the Republic of Chile. The Joint ALMA Observatory is operated by ESO, AUI/NRAO and NAOJ. The SMA is a joint project between the Smithsonian Astrophysical Observatory and the Academia Sinica Institute of Astronomy and Astrophysics and is funded by the Smithsonian Institution and the Academia Sinica.

Aim Diverticulitis is a common cause for acute surgical admissions. UK guidance recommends uncomplicated diverticulitis is managed with antibiotics, and follow-up outpatient lower gastrointestinal (LGI) endoscopy (flexible sigmoidoscopy or colonoscopy) arranged 6-8 weeks after discharge. This audit aimed to assess compliance to national guidance and assess adenoma detection rate. Method Retrospective analysis of discharge summaries coded ‘diverticulitis’ from January 2017 – April 2020 at University Hospital Bristol(UHB). Results 426 patients presented with uncomplicated diverticulitis, mean age 60.5 years (22-92 years). 42% (179/426) of patients underwent LGI endoscopy as an inpatient or on discharge. Median time to outpatient endoscopy was 70 days (6-287 days). 23% (99/426) had LGI endoscopy within the 8-week target. Histology showed: 21% (37/179) polyp; 5% (9/179) tubular adenoma; and one patient had high grade dysplasia. The histology for the remaining 28 patients with polyps showed: hyperplasia; granulation tissue; inflammation; or samples were not sent for histology. No cases of malignancy were detected. Conclusions 58% of patients admitted with acute uncomplicated diverticulitis did not have a follow-up LGI endoscopy and only 23% had LGI endoscopy within the 8-week target. 21% had a polyp with a 5% rate of tubular adenoma and no cases of malignancy. UHB needs to improve compliance with national guidance for the arrangement of follow-up LGI endoscopy, however the absence of detection of malignancy raises the question of whether we need to re-consider its necessity for patients with uncomplicated diverticulitis.

We report the earliest detection of the 19.967-GHz [transition 21–30E (t = 0)] methanol maser associated with the massive star-forming region G358.93–0.03. The flare was detectable from 2019 January 23 to March 5, for only 44 d. It turned out to be the most powerful 19.967-GHz maser in the Galaxy in the entire history of observations, taking into account the 104-Jy flux from it on the Earth’s surface and the distance to the source, 6.75 kpc. The 19.967-GHz maser flared contemporaneously with the first of two flares detected in associated 20.971-GHz methanol masers. We estimated that the ratio of flux densities between these two transitions is F20.971/F19.967 = 14 ± 4, increasing to >520 in the second flare. We discuss the differences between the two flares in the 20.971-GHz methanol masers and the consequence thereof.

Regionalization of complex surgical care results in increasing need for patients to travel for complex oncologic procedures such as cystectomy in bladder cancer. We examined the association between travel distance to a cystectomy center, readmission, and survival.Using Surveillance, Epidemiology, and End Results (SEER)-Medicare data, we identified bladder cancer patients undergoing radical cystectomy during 2004-2011. Patients were grouped into quartiles of distance to cystectomy center in miles (6 [close], 6-16.9 [moderately close], 17-47.9 [moderately far], ≥ 48 [far]). Multivariable logistic regression, accounting for clustering within hospitals, was used to assess the association between travel distance and readmission. A secondary analysis examined the association between travel distance and survival using multivariable proportional hazard regression.Among 4556 patients who underwent cystectomy, 1857 (41%) were readmitted, and 1251 (67%) of readmissions were to the index hospital. With increasing travel distance there was no significant difference in the overall rate of 90-day readmission. However, the farther a patient traveled, the lower the odds of being readmitted to the index hospital (adjusted odds ratio [95% confidence interval] as follows: moderately close, 0.43 miles [0.29-0.63]; moderately far, 0.14 miles [0.10-0.19]; and far, 0.07 [0.05-0.11]). Increasing travel distance was associated with improved survival.With greater distance traveled to a cystectomy center, rates of readmission to nonindex centers increased. Survival differences may be explained by the impact of travel burden on processes of care and case mix. Future efforts should focus on improving care coordination between index and nonindex hospitals and ensuring equitable access to cystectomy and other critical cancer services.

Objective To model the risk of radiation-induced malignancy from computed tomography urography (CTU) in evaluation of gross hematuria and contrast this with the benefits of urinary tract cancer detection when compared to renal ultrasound. Methods A PUBMED-based literature search was performed to identify model inputs. Estimates of radiation-induced malignancy rates were obtained from the Biological Effects of Ionizing Radiation VII report with dose extrapolation using the linear no-threshold model. Results Male gender and age over 50 years were associated with a relative risk of upper tract malignancy of 2.04 and 2.95, respectively. The risk of upper tract malignancy missed by renal ultrasound ranged from 0.055% in females under 50 to 0.51% in males over 50. Risk of CTU-induced malignancy with associated loss of life expectancy ranged from 0.25% and 0.027 years in females under 50 to 0.08% and 0.0054 years in males over 50. For CTU to be superior to renal ultrasound, an undiagnosed upper tract malignancy would have to carry a loss of life expectancy of 49.2 years in females under 50, 13.4 years in males under 50, 2.6 years in females over 50, and 1.1 years in males over 50. Conclusion In low-risk patients, CTU for evaluation of gross hematuria may carry a significant risk of radiation-induced secondary malignancy relative to the diagnostic benefit offered over renal ultrasound

We have investigated the methanol CH3OH lines at frequencies of 19.967 GHz [21-30 E(vt = 0) transition] and 20.971 GHz [101-112 E+(vt = 1) transition] toward the massive region of active star formation G358.931-0.030 with the RT-22 (Simeiz) and RT-26 (HartRAO) radio telescopes. Two new flares have been detected. One of the flares (at 20.971 GHz) is extremely powerful in the frequency range 192-26 GHz. We present our monitoring of the flaring events detected at 19.967 and 20.971 GHz. The time dependence of the flare amplitude reflects the complex structure of the maser emission regions. The velocity structure of the flares is considered.

Trends in population abundance can be challenging to quantify during range expansion and contraction, when there is spatial variation in trend, or the conservation area is large. We used genetic detection data from natural bear rubbing sites and spatial capture-recapture (SCR) modeling to estimate local density and population growth rates in a grizzly bear population in northwestern Montana, USA. We visited bear rubs to collect hair in 2004, 2009—2012 (3,579—4,802 rubs) and detected 249—355 individual bears each year. We estimated the finite annual population rate of change 2004—2012 was 1.043 (95% CI = 1.017—1.069). Population density shifted from being concentrated in the north in 2004 to a more even distribution across the ecosystem by 2012. Our genetic detection sampling approach coupled with SCR modeling allowed us to estimate spatially variable growth rates of an expanding grizzly bear population and provided insight into how those patterns developed. The ability of SCR to utilize unstructured data and produce spatially explicit maps that indicate where population change is occurring promises to facilitate the monitoring of difficult-to-study species across large spatial areas.

We report the detection of new 12.178, 12.229, 20.347, and 23.121 GHz methanol masers in the massive star-forming region G358.93-0.03, which are flaring on similarly short timescales (days) as the 6.668 GHz methanol masers also associated with this source. The brightest 12.178 GHz channel increased by a factor of over 700 in just 50 d. The masers found in the 12.229 and 20.347 GHz methanol transitions are the first ever reported and this is only the fourth object to exhibit associated 23.121 GHz methanol masers. The 12.178 GHz methanol maser emission appears to have a higher flux density than that of the 6.668 GHz emission, which is unusual. No associated near-infrared flare counterpart was found, suggesting that the energy source of the flare is deeply embedded., 9 pages, 3 figures, 2 tables, Published in MNRAS

The prostate biopsy pathology report represents a critical document used for decision-making in patients diagnosed with prostate cancer, yet the content exceeds the health literacy of most patients. We sought to create and compare the effectiveness of a patient-centered prostate biopsy report compared with standard reports. Using a modified Delphi approach, prostate cancer experts identified critical components of a prostate biopsy report. Patient focus groups provided input for syntax and formatting of patient-centered pathology reports. Ninety-four patients with recent prostate biopsies were block randomized to the standard report with or without the patient-centered report. We evaluated patient activation, self-efficacy, provider communication skills, and prostate cancer knowledge. Experts selected primary and secondary Gleason score and the number of positive scores as the most important elements of the report. Patients prioritized a narrative design, non-threatening language and information on risk classification. Initial assessments were completed by 87% (40/46) in the standard report group and 81% (39/48) in the patient-centered report group. There were no differences in patient activation, self-efficacy, or provider communication skills between groups. Patients who received the patient-centered report had significantly improved ability to recall their Gleason score (100% vs. 85%, p = 0.026) and number of positive cores (90% vs. 65%, p = 0.014). In total, 86% of patients who received the patient-centered report felt that it helped them better understand their results and should always be provided. Patient-centered pathology reports are associated with significantly higher knowledge about a prostate cancer diagnosis. These important health information documents may improve patient-provider communication and help facilitate shared decision-making among patients diagnosed with prostate cancer.

OBJECTIVE: To characterize the use of multiparametric magnetic resonance imaging (mpMRI) in male Medicare beneficiaries electing active surveillance for prostate cancer. Multi-parametric resonance imaging (mpMRI) has emerged as a tool that may improve risk-stratification and decrease repeated biopsies in men electing active surveillance. However, the extent to which mpMRI has been implemented in active surveillance has not been established. METHODS: Using Surveillance, Epidemiology, and End Results (SEER) registry data linked to Medicare claims data, we identified men with localized prostate cancer diagnosed between 2008–2013 and managed with active surveillance. We classified men into two treatment groups: active surveillance without mpMRI and active surveillance with mpMRI. We then fit a multivariable logistic regression models to examine changing mpMRI utilization over time, and factors associated with the receipt of mpMRI. RESULTS: We identified 9,467 men on active surveillance. Of these, 8,178 (86%) did not receive mpMRI and 1,289 (14%) received mpMRI. The likelihood of receiving mpMRI over the entire study period increased by 3.7% (p=0.004). On multivariable logistic regression, patients who were younger, white, had lower comorbidity burden, lived in the northeast and west, had higher incomes and lived in more urban areas had greater odds of receiving mpMRI (all p

Highlights • A novel dual route vaccination using the MERS-CoV RBD sub-unit has been developed. • Murine antisera induced to the RBD protein , were neutralising in vitro. • MERS-CoV susceptibility was induced in naïve mice with Ad5hDPP4. • Passive transfer of anti-RBD sera protected susceptible mice. • Protected mice had a significantly reduced viral titre (P = 0.02) in their lungs., Murine antisera with neutralising activity for the coronavirus causative of Middle East respiratory syndrome (MERS) were induced by immunisation of Balb/c mice with the receptor binding domain (RBD) of the viral Spike protein. The murine antisera induced were fully-neutralising in vitro for two separate clinical strains of the MERS coronavirus (MERS-CoV). To test the neutralising capacity of these antisera in vivo, susceptibility to MERS-CoV was induced in naive recipient Balb/c mice by the administration of an adenovirus vector expressing the human DPP4 receptor (Ad5-hDPP4) for MERS-CoV, prior to the passive transfer of the RBD-specific murine antisera to the transduced mice. Subsequent challenge of the recipient transduced mice by the intra-nasal route with a clinical isolate of the MERS-CoV resulted in a significantly reduced viral load in their lungs, compared with transduced mice receiving a negative control antibody. The murine antisera used were derived from mice which had been primed sub-cutaneously with a recombinant fusion of RBD with a human IgG Fc tag (RBD-Fc), adsorbed to calcium phosphate microcrystals and then boosted by the oral route with the same fusion protein in reverse micelles. The data gained indicate that this dual-route vaccination with novel formulations of the RBD-Fc, induced systemic and mucosal anti-viral immunity with demonstrated in vitro and in vivo neutralisation capacity for clinical strains of MERS-CoV.

—Powerful flares in Galactic kilomasers are closely associated with regions of intense star formation. They contribute to the elucidation of physical processes occurring in these structures. We have recorded a superpowerful flare in the high-velocity −81 km s−1 line in the Galactic maser source W49N. As a result of our monitoring at the RT-22 (Simeiz), RT-32 (Torun), RT-100 (Effelsberg), and RT-32 (Medicina) radio telescopes in the period from September 2017 to November 2018, we have obtained the shape of the spectral flux density variations in the source with time. At the peak the flux density reached P ≈ 5 × 10^4 Jy. The flare has a double pattern and different durations of its components. The pattern of spectral flux density variations for the first flare with a considerably shorter duration is apparently related to a sharp increase in the density of the medium and the photon flux and to a significant rise in the temperature to hundreds of kelvins. We propose a mechanism of primary energy release related to the existence of close massive multiple systems in star-forming regions. A powerful gravitational perturbation at the system’s periastron can lead to a partial ejection of the envelope of the central massive star in a direction close to the major axis of the ellipse of the companion’s orbit. This explains the significant asymmetry of high-velocity lines in W49N. The ejected envelope is an energy source more significant than the stellar wind and can explain the giant flares in the object. Further comprehensive studies in this direction, including monitoring VLBI studies, are needed to confirm this assumption.

Objectives To describe the rate and determinants of palliative care use amongst Medicare beneficiaries with bladder cancer and encourage a national dialogue on improving coordinated urological, oncological, and palliative care in patients with genitourinary malignancies. Patients and methods Using Surveillance, Epidemiology, and End Results-Medicare data, we identified patients diagnosed with muscle-invasive bladder cancer (MIBC) between 2008 and 2013. Our primary outcome was receipt of palliative care, defined as the presence of a claim submitted by a Hospice and Palliative Medicine subspecialist. We examined determinants of palliative care use using logistic regression analysis. Results Over the study period, 7303 patients were diagnosed with MIBC and 262 (3.6%) received palliative care. Of 2185 patients with advanced bladder cancer, defined as either T4, N+ , or M+ disease, 90 (4.1%) received palliative care. Most patients that received palliative care (>80%, >210/262) did so within 24 months of diagnosis. On multivariable analysis, patients receiving palliative care were more likely to be younger, female, have greater comorbidity, live in the central USA, and have undergone radical cystectomy as opposed to a bladder-sparing approach. The adjusted probability of receiving palliative care did not significantly change over time. Conclusions Palliative care provides a host of benefits for patients with cancer, including improved spirituality, decrease in disease-specific symptoms, and better functional status. However, despite strong evidence for incorporating palliative care into standard oncological care, use in patients with bladder cancer is low at 4%. This study provides a conservative baseline estimate of current palliative care use and should serve as a foundation to further investigate physician-, patient-, and system-level barriers to this care.

The COVID-19 pandemic has led to a reduced colonoscopy capacity in the UK resulting in increased waiting times for investigation. To increase diagnostic capacity and reduce the risk of diagnostic delay, CT colonography (CTC) and colon capsule endoscopy (CCE) are increasingly being relied upon. Endoscopic assessment and treatment will be required for those patients with large colonic polyps or malignant tumours detected by CTC or CCE, provided they are fit enough to undergo further investigation. The management of patients with intermediate (6-9mm) and diminutive (

In recent years, dramatic outbursts have been identified toward massive protostars via infrared and millimeter dust continuum and molecular maser emission. The longest lived outburst ($>6$ yr) persists in NGC6334I-MM1, a deeply-embedded object with no near-IR counterpart. Using FORCAST and HAWC+ on SOFIA, we have obtained the first mid-infrared images of this field since the outburst began. Despite being undetected in pre-outburst ground-based 18 $��$m images, MM1 is now the brightest region at all three wavelengths (25, 37, and 53 $��$m), exceeding the ultracompact HII region MM3 (NGC6334F). Combining the SOFIA data with ALMA imaging at four wavelengths, we construct a spectral energy distribution of the combination of MM1 and the nearby hot core MM2. The best-fit Robitaille radiative transfer model yields a luminosity of $(4.9\pm0.8)\times10^4 L_\odot$. Accounting for an estimated pre-outburst luminosity ratio MM1:MM2 = $2.1\pm0.4$, the luminosity of MM1 has increased by a factor of $16.3\pm4.4$. The pre-outburst luminosity implies a protostar of mass 6.7 $M_\odot$, which can produce the ionizing photon rate required to power the pre-outburst hypercompact HII region surrounding the likely outbursting protostar MM1B. The total energy and duration of the outburst exceed the S255IR-NIRS3 outburst by a factor of $\gtrsim3$, suggesting a different scale of event involving expansion of the protostellar photosphere (to $\gtrsim$ 20 $R_\odot$), thereby supporting a higher accretion rate ($\gtrsim$0.0023 $M_\odot$ yr$^{-1}$) and reducing the ionizing photon rate. In the grid of hydrodynamic models of Meyer et al. 2021, the combination of outburst luminosity and magnitude (3) places the NGC6334I-MM1 event in the region of moderate total accretion ($\sim$0.1-0.3 $M_\odot$) and hence long duration ($\sim$40-130 yr)., 11 pages, 3 figures, 2 tables; accepted for publication in The Astrophysical Journal Letters

Basal-like breast cancer (BLBC) is an aggressive and deadly subtype of human breast cancer that is highly metastatic, displays stem-cell like features, and has limited treatment options. Therefore, developing and characterizing preclinical mouse models with tumors that resemble BLBC is important for human therapeutic development. ATF3 is a potent oncogene that is aberrantly expressed in most human breast cancers. In the BK5.ATF3 mouse model, overexpression of ATF3 in the basal epithelial cells of the mammary gland produces tumors that are characterized by activation of the Wnt/β-catenin signaling pathway. Here, we used RNA-Seq and microRNA (miRNA) microarrays to better define the molecular features of BK5.ATF3-derived mammary tumors. These analyses showed that these tumors share many characteristics of human BLBC including reduced expression of Rb1, Esr1, and Pgr and increased expression of Erbb2, Egfr, and the genes encoding keratins 5, 6, and 17. An analysis of miRNA expression revealed reduced levels of Mir145 and Mir143, leading to the upregulation of their target genes including both the pluripotency factors Klf4 and Sox2 as well as the cancer stem-cell-related gene Kras. Finally, we show through knock-down experiments that ATF3 may directly modulate MIR145/143 expression. Taken together, our results indicate that the ATF3 mouse mammary tumor model could provide a powerful model to define the molecular mechanisms leading to BLBC, identify the factors that contribute to its aggressiveness, and, ultimately, discover specific genes and gene networks for therapeutic targeting.

Class II methanol masers are signs of massive young stellar objects (MYSOs). Recent findings show that MYSO accretion bursts cause flares of these masers. Thus, maser monitoring can be used to identify such bursts. Burst-induced SED changes provide valuable information on a very intense phase of high-mass star formation. In mid-January 2019, a maser flare of the MYSO G358.93-0.03 was reported. ALMA and SMA imaging resolved the core of the star forming region and proved the association of the masers with the brightest continuum source MM1. However, no significant flux rise of the (sub)mm dust continuum was found. Thus, we performed NIR imaging with GROND and IFU spectroscopy with FIFI-LS aboard SOFIA to detect possible counterparts to the (sub)mm sources, and compare their photometry to archival measurements. The comparison of pre-burst and burst SEDs is of crucial importance to judge whether a luminosity increase due to the burst is present and if it triggered the maser flare. The FIR fluxes of MM1 measured with FIFI-LS exceed those from Herschel significantly, which clearly confirms the presence of an accretion burst. The second epoch data, taken about 16 months later, still show increased fluxes. Our RT modeling yielded major burst parameters and suggests that the MYSO features a circumstellar disk which might be transient. From the multi-epoch SEDs, conclusions on heating and cooling time-scales could be drawn. Circumstances of the burst-induced maser relocation have been explored. The verification of the accretion burst from G358 is another confirmation that Class II methanol maser flares represent an alert for such events. The few events known to date already indicate that there is a broad range in burst strength and duration as well as environmental characteristics. The G358 event is the shortest and least luminous MYSO accretion burst so far., Comment: 22 pages, 11 figures, accepted by A&A. Abstract abridged for arxiv submission

Epilepsy affects all ages, races, genders, and socioeconomic groups. In about one third of patients, epilepsy is uncontrolled with current medications, leaving a vast need for improved therapies. The causes of epilepsy are diverse and not always known but one gene mutated in a small subpopulation of patients is phosphatase and tensin homolog (PTEN). Moreover, focal cortical dysplasia, which constitutes a large fraction of refractory epilepsies, has been associated with signaling defects downstream of PTEN. So far, most preclinical attempts to reverse PTEN deficiency-associated neurological deficits have focused on mTOR, a signaling hub several steps downstream of PTEN. Phosphoinositide 3-kinases (PI3Ks), by contrast, are the direct enzymatic counteractors of PTEN, and thus may be alternative treatment targets. PI3K activity is mediated by four different PI3K catalytic isoforms. Studies in cancer, where PTEN is commonly mutated, have demonstrated that inhibition of only one isoform, p110β, reduces progression of PTEN-deficient tumors. Importantly, inhibition of a single PI3K isoform leaves critical functions of general PI3K signaling throughout the body intact. Here, we show that this disease mechanism-targeted strategy borrowed from cancer research rescues or ameliorates neuronal phenotypes in male and female mice with neuron-specific PTEN deficiency. These phenotypes include cell signaling defects, protein synthesis aberrations, seizures, and cortical dysplasia. Of note, p110β is also dysregulated and a promising treatment target in the intellectual disability Fragile X syndrome, pointing towards a shared biological mechanism that is therapeutically targetable in neurodevelopmental disorders of different etiologies. Overall, this work advocates for further assessment of p110β inhibition not only in PTEN deficiency-associated neurodevelopmental diseases but also other brain disorders characterized by defects in the PI3K/mTOR pathway.

Aim The coronavirus pandemic has led to significant challenges for healthcare delivery across the globe. Non-emergency endoscopic activity in the UK has been postponed, raising concerns of increased delays in the diagnosis of colorectal cancer and a surge in demand once services resume. Measures to mitigate this risk must be considered. Method This paper reviews various investigative modalities for colorectal disease which could be deployed during cessation of colonoscopy services. We focus on colon capsule endoscopy (CCE) due to its relevance during the COVID-19 pandemic and its ability to triage patients effectively to further endoscopic investigations. Results CT of the abdomen and pelvis has been suggested as a triage tool while access to colonoscopy is limited. However, CT may lead to the spread of COVID-19 as patients attend the hospital, and it exposes them to the risks of radiation. Faecal immunochemistry tests have been demonstrated as a good predictor of colonic pathology and could be safely used to risk stratify patients when prioritizing colonoscopy. CCE is a safe and innovative technology for investigating the colon. Procedures can be carried out in the community and can be conducted safely during the coronavirus pandemic. It has been shown to be an accurate detector of colonic neoplasia and can reduce demand for colonoscopy. Conclusion As colonoscopy services resume, they will probably experience high demand leading to further delays for patients. CCE could be used to reduce the number of patients requiring colonoscopy and triage those requiring further endoscopic investigations appropriately.

Objective To examine the use of prescription opioids in patients undergoing major prostate and kidney operations. Methods This is a prospective observational study that includes opioid naive patients who underwent a major prostate or kidney operation from January 2017-May 2017. A telephone survey was conducted 3-4 weeks postoperatively. The survey assessed the number of 5 mg oxycodone-equivalents prescribed, opioid use, and disposal. Results A total of 155 patients were included in our analysis. Most patients were male (86%), most were married (74%), the median was age 64 (interquartile range 59-70), and the majority were Caucasian (84%). Most patients reported social alcohol use (56%), but most denied current tobacco use (77%) or current and/or previous drug use (76%). Opioid prescribing exceeded use from 1.9- to 6.8-fold for all procedural categories. Overall, a total of 4065 oxycodone-equivalents were prescribed during this study and 60% of pills prescribed went unused. This resulted in 2622 excess pills in the community. Conclusion Opioids are prescribed far in excess of need following major open and minimally invasive urologic procedures. Overall, 60% of prescribed opioids were unused. These data provide initial benchmarks for appropriate opioid prescribing after major prostate and kidney procedures. Future work to validate this initial guideline and improve patient counseling regarding appropriate perioperative opioid use and disposal is needed.

The results of long-term monitoring of the Galactic maser source IRAS 18316-0602 (G25.65+1.05) in the water-vapor line at frequency f = 22.235 GHz (6_16-5_23 transitioin) carried out on the 22-m Simeiz, 26-m HartRAO, and 26-m Torun radio telescopes are reported. The source has been episodically observed on the Simeiz telescope since 2000, with more regular observations beginning in 2017. A double flare was observed beginning in September 2017 and continuing to February 2018, which was the most powerful flare registered over the entire history of observations of this object. Most of the monitoring of the flare was carried out in a daily regime. Detailed analysis of the variations of the flux density, which reached a maximum value P ≈ 1.3 × 10^5 Jy, have led to important scientific conclusions about possible mechanisms for the emission in this water line. The exponential growth in the flux density in this double flare testifies that it was associated with a maser that was unsaturated right up to the maximum flux densities observed. An additional argument suggesting the maser was unsaturated is the relatively moderate degree of linear polarization (≈30%), nearly half the value displayed by the Galactic kilomasers in Orion KL. The accurate distance estimate for IRAS 18316-0602 (12.5 kpc) and the flux density at the flare maximum (≈1.3 × 10^5 Jy) makes this the most powerful Galactic kilomaser known. The double form of the flare with exponential rises in flux density rules out the possibility that the flare is the effect of directivity of a radiation beam relative to the observer. The physical nature of the flare is most likely related to internal parameters of the medium in which the maser clumps radiating in the water line are located. A rapid, exponential growth in the flux density of a kilomaser and associated exponential decays requires the presence of an explosive increase in the density of the medium and the photon flux, leading to an increase in the temperature by 10-40 K above the initial base level. A mechanism for the primary energy release in IRAS 18316-0602 is proposed, which is associated with a multiple massive star system located in a stage of evolution preceding its entry onto the main sequence. A flare in this object could initiate gravitational interaction between the central star and a massive companion at its periastron. The resulting powerful gravitational perturbation could lead to the ejection of the envelope of the central supermassive star, which gives rise to an explosive increase in the density and temperature of the associate gas-dust medium when it reaches the disk, where the maser clumps are located.

INTRODUCTION AND OBJECTIVE:The impetus toward robust linkage between patient-centered, high quality care and reimbursement continues to gain traction with the advent of alternative payment models, ...

Surgeons play a pivotal role in combating the opioid crisis that currently grips the United States. Changing surgeon behavior is difficult, and the degree to which behavioral science can steer surgeons toward decreased opioid prescribing is unclear.This was a single-institution, single-arm, pre- and postintervention study examining the prescribing of opioids by urologists for adult patients undergoing prostatectomy or nephrectomy. The primary outcome was the quantity of opioids prescribed in oral morphine equivalents (OMEs) after hospital discharge. The primary exposure was a multipronged behavioral intervention designed to decrease opioid prescribing. The intervention had 3 components: 1) formal education, 2) individual audit feedback, and 3) peer comparison performance feedback. There were 3 phases to the study: a pre-intervention phase, an intervention phase, and a washout phase.Three hundred eighty-two patients underwent prostatectomy, and 306 patients underwent nephrectomy. The median OMEs decreased from 195 to 19 in the prostatectomy patients and from 200 to 0 in the nephrectomy patients (P.05 for both). The median OMEs prescribed did not increase during the washout phase. Prostatectomy patients discharged with opioids had higher levels of anxiety than patients discharged without opioids (P.05). Otherwise, prostatectomy and nephrectomy patients discharged with and without opioids did not differ in their perception of postoperative pain management, activity levels, psychiatric symptoms, or somatic symptoms (P.05 for all).Implementing a multipronged behavioral intervention significantly reduced opioid prescribing for patients undergoing prostatectomy or nephrectomy without compromising patient-reported outcomes.

The AUA (American Urological Association) guidelines for asymptomatic microscopic hematuria recommend that patients undergo computerized tomography urography, which is associated with high doses of ionizing radiation. To our knowledge the associated risk of secondary malignancy and mortality remains unknown. We modeled the risk of malignancy and associated mortality due to ionizing radiation from computerized tomography urography relative to the additional diagnostic benefit offered over renal ultrasound.We performed a PubMed® based literature search to identify model inputs. We obtained estimates of age and gender specific radiation induced secondary malignancy and mortality rates from the BEIR (Biologic Effects of Ionizing Radiation) VII Phase 2 report with dose extrapolation using the linear no threshold model.Patients with asymptomatic microscopic hematuria had a 0.053% and 0.48% prevalence of upper tract urothelial carcinoma and renal cell carcinoma, respectively. Ultrasound had 77% sensitivity for upper tract urothelial carcinoma and 82% sensitivity for renal cell carcinoma. The effective radiation dose of computerized tomography urography was 31.7 mSv. Based on these inputs a population of 100,000 patients with asymptomatic microscopic hematuria would include 53.1 and 478 patients with upper tract urothelial carcinoma and renal cell carcinoma, respectively. On ultrasound alone 98.2 cases of upper urinary tract malignancy would be missed. An additional 149 cases of secondary malignancy would be caused by computerized tomography urography associated radiation with 101 fatalities. A total of 1,018.3 computerized tomography urography studies would need to be performed to detect an additional case of upper tract malignancy.Based on current risk models computerized tomography urography for asymptomatic microscopic hematuria may be associated with a small but significant risk of secondary malignancy relative to the additional diagnostic benefit offered.

Aims Intensity-modulated radiotherapy (IMRT) is increasingly used in the treatment delivery of chemoradiotherapy in anal cancer with the ability to reduce toxicity. We report on 4 year outcomes since the introduction of IMRT and identify the most predictive bowel organ at risk that correlates with acute diarrhoea. Materials and methods Fifty-eight patients receiving definitive chemoradiotherapy for squamous or basaloid cell anal carcinoma (T1-4NanyM0) were reviewed. Fifty-four per cent of patients had stage III disease and most (79%) were treated with a dose of 54 Gy in 30 fractions. Patient acute gastrointestinal toxicity was recorded using Common Terminology Criteria of Adverse Events (CTCAE) diarrhoea grading. Four different methods of bowel were re-contoured for each patient and correlated with acute diarrhoea. Locoregional control and overall survival were analysed. Results CTCAE grade 3 or more diarrhoea occurred in 11/58 patients (19%). Seven patients did not complete treatment; 10 patients (17%) required a treatment break of 3 or more days. ‘Bowel cavity’ was the best predictor of acute grade 3 toxicity using volume (P = 0.002) or volume to bowel cavity in 5 Gy bins (V5–V50Gy); P 300 cm3 predicts a 42% risk. Four year progression-free survival was 84% (95% confidence interval 73–92%) and overall survival was 88% (95% confidence interval 75–95%). Conclusion Chemoradiation using IMRT provides excellent local control and acceptable acute gastrointestinal toxicity. Bowel cavity is the most sensitive predictor for grade 3 versus grade 0–2 diarrhoea, with any volume receiving 5–50 Gy discriminatory.

Years ago, while attending Brooklyn College, I had a professor named Foster Hirsch. Hirsch, one of the leading film scholars in the country, most especially in film noir, has an extensive knowledge...

Our 2015-2016 ALMA 1.3 to 0.87 mm observations (resolution ~200 au) of the massive protocluster NGC6334I revealed that an extraordinary outburst had occurred in the dominant millimeter dust core MM1 (luminosity increase of 70×) when compared with earlier SMA data. The outburst was accompanied by the flaring of ten maser transitions of three species. We present new results from our recent JVLA observations of Class II 6.7 GHz methanol masers and 6 GHz excited OH masers in this region. Class II masers had not previously been detected toward MM1 in any interferometric observations recorded over the past 30 years that targeted the bright masers toward other members of the protocluster (MM2 and MM3=NGC6334F). Methanol masers now appear both toward and adjacent to MM1 with the strongest spots located in a dust cavity ~1 arcsec (1300 au) north of the MM1B hypercompact HII region. In addition, new excited OH masers appear on the non-thermal source CM2. These data reveal the dramatic effects of episodic accretion onto a deeply-embedded high mass protostar and demonstrate its ongoing impact on the surrounding protocluster.

We present subarcsecond resolution pre- and post-outburst JVLA continuum and water maser observations of the massive protostellar outburst source NGC6334I-MM1. The continuum data at 5 and 1.4 cm reveal that the free-free emission powered by MM1B, modeled as a hypercompact HII region from our 2011 JVLA data, has dropped by a factor of 5.4. Additionally, the water maser emission toward MM1, which had previously been strong (500 Jy) has dramatically reduced. In contrast, the water masers in other locations in the protocluster have flared, with the strongest spots associated with CM2, a non-thermal radio source that appears to mark a shock in a jet emanating 2″ (2600 au) northward from MM1. The observed quenching of the HCHII region suggests a reduction in uv photon production due to bloating of the protostar in response to the episodic accretion event.