High early mortality following percutaneous nephrostomy in metastatic cancer: a national analysis of outcomes.

OBJECTIVES: To assess the outcomes of percutaneous nephrostomy in England for renal decompression, in the context of metastatic cancer. METHODS: Retrospective observational study of all patients undergoing nephrostomy with a diagnosis of metastatic cancer from 2010 to 2019 in England, identified and followed up within Hospital Episode Statistics.The primary outcome measure was mortality (14-day and 30-day postprocedure). Secondary outcomes included subsequent chemotherapy or surgery and direct complications of nephrostomy. RESULTS: 10 932 patients were identified: 58.0% were male, 51.0% were >70 years old and 57.7% had no relevant comorbidities (according to Charlson's criteria, other than cancer).1 in 15 patients died within 14 days of nephrostomy and 1 in 6 died within 30 days. Factors associated with higher 30-day mortality were the presence of comorbidities (Charlson score 1-4 (OR 1.27, 95% CI 1.08 to 1.50, p=0.003), score 5+ (OR 1.29, 95% CI 1.14 to 1.45), p<0.001)); inpatient nephrostomy (OR 3.76, 95% CI 2.75 to 5.14, p<0.001) and admitted under the care of specialities of internal medicine (OR 2.10, 95% CI 1.84 to 2.40, p<0.001), oncology (OR 1.80, 95% CI 1.51 to 2.15, p<0.001), gynaecology/gynaeoncology (OR 1.66, 95% CI 1.21 to 2.28, p=0.002) or general surgery (OR 1.62, 95% CI 1.32 to 1.98, p<0.001)), compared with urology.25.4% received subsequent chemotherapy. Receiving chemotherapy was associated with younger patients (eg, age 18-29 (OR 4.04, 95% CI 2.66 to 6.12, p<0.001) and age 30-39 (OR 3.07, 95% CI 2.37 to 3.97, p<0.001)) and under the care of oncology (OR 1.60, 95% CI 1.40 to 1.83, p<0.001) or gynaecology/gynaeoncology (OR 1.64, 95%CI 1.28 to 2.10, p<0.001) compared with urology.43.8% had subsequent abdominopelvic surgery. Not receiving surgery was associated with inpatient nephrostomy (OR 0.82, 95%CI 0.72 to 0.95,p=0.007): non-genitourinary cancers (eg, gynaecology/gynaeoncology cancer (OR 0.86, 95% CI 0.74 to 0.99, p=0.037)); and under the care of a non-surgical specialty (medicine (OR 0.69, 95% CI 0.63 to 0.77, p<0.001), oncology (OR 0.58, 95% CI 0.51 to 0.66, p<0.001)).24.5% of patients had at least one direct complication of nephrostomy: 12.5% required early exchange of nephrostomy, 8.1% had bleeding and 6.7% had pyelonephritis. CONCLUSIONS: The decision to undertake nephrostomy in patients with poor prognosis cancer is complex and should be undertaken in a multidisciplinary team setting. Complication rates are high and minimal survival benefit is derived in many patients, especially in the context of emergency inpatient care.

Source contribution of black carbon aerosol during 2020-2022 at an urban site in Indo-Gangetic Plain.

The extensive emissions of black carbon (BC) from the Indo-Gangetic Plain (IGP) region of India have been well recognized. Particularly, biomass emissions from month-specific crop-residue burning (April, May, October, November) and heating activities (December-February) are considered substantial contributors to BC emissions in the IGP. However, their precise contribution to ambient BC aerosol has not been quantified yet and remains an issue of debate. Therefore, this study aims to fill this gap by quantifying the contribution of these month-specific biomass emissions to ambient BC at an urban site in IGP. This study presents the analysis of BC mass concentrations (MBC) measured for 3 years (2020-2022) in Delhi using an optical photometer i.e., continuous soot monitoring system (COSMOS). A statistical analysis of monthly mean MBC and factors affecting the MBC (ventilation coefficients, air mass back trajectories, fire counts) is performed to derive month-wise contribution due to background concentration, conventional emission, regional transport, crop-residue burning, and heating activities. The yearly mean MBC (5.3 ± 4.7, 5.6 ± 5.0, and 5.3 ± 3.5 µg m-3 during 2020, 2021, and 2022, respectively) remained relatively consistent with repetitive monthly patterns in each year. The peak concentrations were observed from November to January and low concentrations from June to September. Anthropogenic activities contributed significantly to MBC over Delhi with background concentration contributing only 30 % of observed MBC. The percentage contribution of emissions from crop-residue burning varied from 15 % (May) to 37 % (November), while the contribution from heating activities ranged from 25 % (December) to 39 % (January). This source quantification study highlights the significant impact of month-specific biomass emissions in the IGP and can play a vital role in better management and control of these emissions in the region.

Rationale and Design of a Phase 2, Double-blind, Placebo-Controlled, Randomized Trial Evaluating AMP Kinase-Activation by Metformin in Focal Segmental Glomerulosclerosis.

Introduction: Focal segmental glomerulosclerosis (FSGS), the most common primary glomerular disease leading to end-stage kidney disease (ESKD), is characterized by podocyte injury and depletion, whereas minimal change disease (MCD) has better outcomes despite podocyte injury. Identifying mechanisms capable of preventing podocytopenia during injury could transform FSGS to an "MCD-like" state. Preclinical data have reported conversion of an MCD-like injury to one with podocytopenia and FSGS by inhibition of AMP-kinase (AMPK) in podocytes. Conversely, in FSGS, AMPK-activation using metformin (MF) mitigated podocytopenia and azotemia. Observational studies also support beneficial effects of MF on proteinuria and chronic kidney disease (CKD) outcomes in diabetes. A randomized controlled trial (RCT) to test MF in podocyte injury with FSGS has not yet been conducted. Methods: We report the rationale and design of phase 2, double-blind, placebo-controlled RCT evaluating the efficacy and safety of MF as adjunctive therapy in FSGS. By randomizing 30 patients with biopsy-confirmed FSGS to MF or placebo (along with standard immunosuppression), we will study mechanistic biomarkers that correlate with podocyte injury or depletion and evaluate outcomes after 6 months. We specifically integrate novel urine, blood, and tissue markers as surrogates for FSGS progression along with unbiased profiling strategies. Results and Conclusion: Our phase 2 trial will provide insight into the potential efficacy and safety of MF as adjunctive therapy in FSGS-a crucial step to developing a larger phase 3 study. The mechanistic assays here will guide the design of other FSGS trials and contribute to understanding AMPK activation as a potential therapeutic target in FSGS. By repurposing an inexpensive agent, our results will have implications for FSGS treatment in resource-poor settings.

EMBIO trial study protocol: left gastric artery embolisation for weight loss in patients living with obesity with a BMI 35-50 kg/m2.

INTRODUCTION: Left gastric artery embolisation (LGAE) is a well-established treatment for major upper gastrointestinal (GI) bleeding when control is not established via upper GI endoscopy and recently has shown promising results for weight loss in small single arm studies. LGAE could be a treatment option in between our current tier-3 and tier-4 services for obesity. EMBIO is a National Institute for Health Research funded trial, a multicentre double-blinded randomised controlled trial between Imperial College National Health Service Trust and University College London Hospital, comparing LGAE versus Placebo procedure. The key aims of the trial is to evaluate LGAE efficacy on weight loss, its mechanism of action, safety profile and obesity-related comorbidities. METHODS AND ANALYSIS: 76 participants will be recruited from the existing tier-3 database after providing informed consent. Key inclusion criteria include adults aged 18-70 with a body mass index 35-50 kg/m2 and appropriate anatomy of the left gastric artery and coeliac plexus on CT Angiogram. Key exclusion criteria included previous major abdominal and bariatric surgery, weight >150 kg, type 2 diabetes on any medications other than metformin and the use of weight modifying medications. Participants will undergo mechanistic visits 1 week prior to the intervention and 3, 6 and 12 months postintervention. Informed consent will be received from each participant and they will be randomised in a 1:1 ratio to left gastric artery embolisation and placebo treatment. Blinding strategies include the use of moderate doses of sedation, visual and auditory isolation. All participants will enter a tier-3 weight management programme postintervention. The primary analysis will estimate the difference between the groups in the mean per cent weight loss at 12 months. ETHICS AND DISSEMINATION: This trial shall be conducted in full conformity with the 1964 Declaration of Helsinki and all subsequent revisions. Local research ethics approval was granted by London-Central Research Ethics Committee, (Reference 19/LO/0509) on 11 October 2019. The Medicines and Healthcare products Regulatory Agency (MHRA) issued the Letter of No Objection on 8 April 2022 (Reference CI/2022/0008/GB). The trial's development and progress are monitored by an independent trial steering committee and data monitoring and ethics committee. The researchers plan to disseminate results at conferences, in peer- reviewed journals as well as lay media and to patient organisations. TRIAL REGISTRATION NUMBER: ISRCTN16158402.

Colchicine and high-intensity rosuvastatin in the treatment of non-critically ill patients hospitalised with COVID-19: a randomised clinical trial.

OBJECTIVE: To evaluate the effect of colchicine and high-intensity rosuvastatin in addition to standard of care on the progression of COVID-19 disease in hospitalised patients. DESIGN: A pragmatic, open-label, multicentre, randomised controlled trial conducted from October 2020 to September 2021. Follow-up was conducted at 30 and 60 days. The electronic medical record was used at all stages of the trial including screening, enrolment, randomisation, event ascertainment and follow-up. SETTING: Four centres in the Yale New Haven Health System. PARTICIPANTS: Non-critically ill hospitalised patients with COVID-19. INTERVENTIONS: Patients were randomised 1:1 to either colchicine plus high-intensity rosuvastatin in addition to standard of care versus standard of care alone. Assigned treatment was continued for the duration of index hospitalisation or 30 days, whichever was shorter. PRIMARY AND SECONDARY OUTCOME MEASURES: The prespecified primary endpoint was progression to severe COVID-19 disease (new high-flow or non-invasive ventilation, mechanical ventilation, need for vasopressors, renal replacement therapy or extracorporeal membrane oxygenation, or death) or arterial/venous thromboembolic events (ischaemic stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism) evaluated at 30 days. RESULTS: Among the 250 patients randomised in this trial (125 to each arm), the median age was 61 years, 44% were women, 15% were Black and 26% were Hispanic/Latino. As part of the standard of care, patients received remdesivir (87%), dexamethasone (92%), tocilizumab (18%), baricitinib (2%), prophylactic/therapeutic anticoagulation (98%) and aspirin (91%). The trial was terminated early by the data and safety monitoring board for futility. No patients were lost to follow-up due to electronic medical record follow-up. There was no significant difference in the primary endpoint at 30 days between the active arm and standard of care arm (15.2% vs 8.8%, respectively, p=0.17). CONCLUSIONS: In this small, open-label, randomised trial of non-critically ill hospitalised patients with COVID-19, the combination of colchicine and rosuvastatin in addition to standard of care did not appear to reduce the risk of progression of COVID-19 disease or thromboembolic events, although the trial was underpowered due to a lower-than-expected event rate. The trial leveraged the power of electronic medical records for efficiency and improved follow-up and demonstrates the utility of incorporating electronic medical records into future trials. TRIAL REGISTRATION: NCT04472611.

Primary Splenic Ectopic Pregnancy Managed With Angioembolization and Splenectomy.

A primary splenic ectopic pregnancy is an extremely rare entity; one that is fraught with life-threatening risks due to potential for acute hemorrhage. The diagnosis is challenging to make, and once detected, there is a distinct sense of urgency to perform operative intervention (splenectomy) prior to any impending rupture. This report describes the case of a 34-year-old female, gravida 5, para 3013, at estimated 4 weeks gestation with a 2.1 × 1.3 cm ectopic pregnancy abutting the splenic hilum. Through multidisciplinary management with Obstetrics/Gynecology (OB/GYN), Interventional Radiology (IR), and General Surgery teams, the patient received preoperative non-elective splenic artery embolization to mitigate risk of rupture, followed by open splenectomy while remaining hemodynamically stable throughout the course of her treatment. As evidenced by this case, a multidisciplinary approach to this unusual clinical presentation leads to successful patient outcomes and prevents the devastating complication of acute hemorrhage.

Highly Sensitive and Specific Detection of Bladder Cancer via Targeted Ultra-deep Sequencing of Urinary DNA.

BACKGROUND: There is an unmet need for an accurate, validated, noninvasive test for diagnosing and monitoring bladder cancer (BC). Detection of BC-associated mutations in urinary DNA via targeted deep sequencing could meet this need. OBJECTIVE: To test the ability of mutational analysis of urinary DNA to noninvasively detect BC within the context of haematuria investigations and non-muscle-invasive BC (NMIBC) surveillance. DESIGN, SETTING, AND PARTICIPANTS: Capture-based ultra-deep sequencing was performed for 443 somatic mutations in 23 genes in 591 urine cell-pellet DNAs from haematuria clinic patients and 293 from NMIBC surveillance patients. Variant calling was optimised to minimise false positives using urine samples from 162 haematuria clinic patients without BC. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The sensitivity and specificity for BC diagnosis were determined. RESULTS AND LIMITATIONS: Mutational analysis of urinary DNA detected 144 of the 165 haematuria patients diagnosed with incident BC from two independent cohorts, yielding overall sensitivity of 87.3% (95% confidence interval [CI] 81.2-92.0%) at specificity of 84.8% (95% CI 79.9-89.0%). The sensitivity was 97.4% for grade 3, 86.5% for grade 2, and 70.8% for grade 1 BC. Among NMIBC surveillance patients, 25 out of 29 recurrent BCs were detected, yielding sensitivity of 86.2% (95% CI 70.8-97.7%) at specificity of 62.5% (95% CI 56.1-68.0%); a positive urine mutation test in the absence of clinically detectable disease was associated with a 2.6-fold increase in the risk of future recurrence. The low number of recurrences in the NMIBC surveillance cohort and the lower sensitivity for detecting grade 1 pTa BC are limitations. CONCLUSIONS: Detection of mutations in a small panel of BC-associated genes could facilitate noninvasive BC testing and expedite haematuria investigations. Following further validation, the test could also play a role in NMIBC surveillance. PATIENT SUMMARY: Identification of alterations in genes that are frequently mutated in bladder cancer appears to be a promising strategy for detecting disease from urine samples and reducing reliance on examination of the bladder via a telescopic camera inserted through the urethra.

Preoperative splenic artery embolization for splenic ectopic pregnancy.

Primary splenic pregnancy is an extremely rare form of extra tubal ectopic pregnancy. Trans-arterial embolization is emerging as an effective treatment for ectopic pregnancy. Here, we present a 34-year-old G4P3003 woman who presented with vaginal bleeding and elevated serum quantitative human chorionic gonadotropin (beta-hCG). After initial workup showed no intrauterine pregnancy, MRI of the abdomen showed an ectopic gestational sac at the splenic hilum. A preoperative splenic artery embolization was performed successfully prior to open splenectomy for removal of the ectopic pregnancy to minimize operative blood loss. By sharing our experience in this case, we contribute to the validation of trans-arterial embolization as an effective adjunctive measure in treating ectopic pregnancy.

The risk of subsequent surgery following bowel resection for Crohn's disease in a national cohort of 19 207 patients.

AIM: Surgery is required for most patients with Crohn's disease (CD) and further surgery may be necessary if medical treatment fails to control disease activity. The aim of this study was to characterize the risk of, and factors associated with, further surgery following a first resection for Crohn's disease. METHODS: Hospital Episode Statistics from England were examined to identify patients with CD and a first recorded bowel resection between 2007 and 2016. Multivariable logistic regression was used to examine risk factors for further resectional surgery within 5 years. Prevalence-adjusted surgical rates for index CD surgery over the study period were calculated. RESULTS: In total, 19 207 patients (median age 39 years, interquartile range 27-53 years; 55% women) with CD underwent a first recorded resection during the study period. 3141 (16%) underwent a further operation during the study period. The median time to further surgery was 2.4 (interquartile range 1.2-4.6) years. 3% of CD patients had further surgery within 1 year, 14% by 5 years and 23% by 10 years. Older age (≥58), index laparoscopic surgery and index elective surgery (adjusted OR 0.65, 95% CI 0.54-0.77; 0.77, 0.67-0.88; and 0.77, 0.69-0.85; respectively) were associated with a reduced risk of further surgery by 5 years. Prior surgery for perianal disease (1.60, 1.37-1.87), an extraintestinal manifestation of CD (1.51, 1.22-1.86) and index surgery in a high-volume centre for CD surgery (1.20, 1.02-1.40) were associated with an increased risk of further surgery by 5 years. A 25% relative and 0.3% absolute reduction in prevalence-adjusted index surgery rates for CD was observed over the study period. CONCLUSIONS: Further surgery following an index operation is common in CD. This risk was particularly seen in patients with perianal disease, extraintestinal manifestations and those who underwent index surgery in a high-volume centre.

Clerkship Chiefs: Introducing Students to the Role of Physician Educator.

As a Clerkship Chief, senior medical students prepare for future roles as physician leaders and future medical educators. The Clerkship Chief elective offers senior students an opportunity to work with junior students on their core clerkships. Chiefs assume an educational leadership role as they mentor and provide supplemental formative feedback to junior students in real time. As educators, Chiefs answer questions, prepare study materials and didactics, and assist clerkship students with time management. This early experience and behind-the-scenes view of medical education may influence attitudes and decisions of senior students in pursuit of education leadership.

A Drosophila model of HPV16-induced cancer reveals conserved disease mechanism.

High-risk human papillomaviruses (HR-HPVs) cause almost all cervical cancers and a significant number of vaginal, vulvar, penile, anal, and oropharyngeal cancers. HPV16 and 18 are the most prevalent types among HR-HPVs and together cause more than 70% of all cervical cancers. Low vaccination rate and lack of molecularly-targeted therapeutics for primary therapy have led to a slow reduction in cervical cancer incidence and high mortality rate. Hence, creating new models of HPV-induced cancer that can facilitate understanding of the disease mechanism and identification of key cellular targets of HPV oncogenes are important for development of new interventions. Here in this study, we used the tissue-specific expression technique, Gal4-UAS, to establish the first Drosophila model of HPV16-induced cancer. Using this technique, we expressed HPV16 oncogenes E5, E6, E7 and the human E3 ligase (hUBE3A) specifically in the epithelia of Drosophila eye, which allows simple phenotype scoring without affecting the viability of the organism. We found that, as in human cells, hUBE3A is essential for cellular abnormalities caused by HPV16 oncogenes in flies. Several proteins targeted for degradation by HPV16 oncoproteins in human cells were also reduced in the Drosophila epithelial cells. Cell polarity and adhesion were compromised, resulting in impaired epithelial integrity. Cells did not differentiate to the specific cell types of ommatidia, but instead were transformed into neuron-like cells. These cells extended axon-like structures to connect to each other and exhibited malignant behavior, migrating away to distant sites. Our findings suggest that given the high conservation of genes and signaling pathways between humans and flies, the Drosophila model of HPV16- induced cancer could serve as an excellent model for understanding the disease mechanism and discovery of novel molecularly-targeted therapeutics.

Mutations in SARS-CoV-2 spike protein impair epitope-specific CD4+ T cell recognition.

CD4+ T cells are essential for protection against viruses, including SARS-CoV-2. The sensitivity of CD4+ T cells to mutations in SARS-CoV-2 variants of concern (VOCs) is poorly understood. Here, we isolated 159 SARS-CoV-2-specific CD4+ T cell clones from healthcare workers previously infected with wild-type SARS-CoV-2 (D614G) and defined 21 epitopes in spike, membrane and nucleoprotein. Lack of CD4+ T cell cross-reactivity between SARS-CoV-2 and endemic beta-coronaviruses suggested these responses arose from naïve rather than pre-existing cross-reactive coronavirus-specific T cells. Of the 17 epitopes located in the spike protein, 10 were mutated in VOCs and CD4+ T cell clone recognition of 7 of them was impaired, including 3 of the 4 epitopes mutated in omicron. Our results indicated that broad targeting of epitopes by CD4+ T cells likely limits evasion by current VOCs. However, continued genomic surveillance is vital to identify new mutations able to evade CD4+ T cell immunity.

Correction: A Web-Based Prostate Cancer-Specific Holistic Needs Assessment (CHAT-P): Multimethod Study From Concept to Clinical Practice.

[This corrects the article DOI: 10.2196/32153.].

A Web-Based Prostate Cancer-Specific Holistic Needs Assessment (CHAT-P): Multimethod Study From Concept to Clinical Practice.

BACKGROUND: Men with prostate cancer experience immediate and long-term consequences of the disease and its treatment. They require both long-term monitoring for recurrence or progression and follow-up to identify and help manage psychosocial and physical impacts. Holistic Needs Assessment aims to ensure patient-centered continuing cancer care. However, paper-based generic tools have had limited uptake within cancer services, and there is little evidence of their impact. With the expansion of remote methods of care delivery and to enhance the value of generic tools, we developed a web-based Composite Holistic Needs Assessment Adaptive Tool-Prostate (CHAT-P) specifically for prostate cancer. OBJECTIVE: This paper described the context, conceptual underpinning, and approach to design that informed the development of CHAT-P, starting from the initial concept to readiness for deployment. Through this narrative, we sought to contribute to the expanding body of knowledge regarding the coproduction process of innovative digital systems with potential for enhanced cancer care delivery. METHODS: The development of CHAT-P was guided by the principles of coproduction. Men with prostate cancer and health care professionals contributed to each stage of the process. Testing was conducted iteratively over a 5-year period. An initial rapid review of patient-reported outcome measures identified candidate items for inclusion. These items were categorized and allocated to overarching domains. After the first round of user testing, further items were added, improvements were made to the adaptive branching system, and response categories were refined. A functioning version of CHAT-P was tested with 16 patients recruited from 3 outpatient clinics, with interviewers adopting the think-aloud technique. Interview transcripts were analyzed using a framework approach. Interviews and informal discussions with health care professionals informed the development of a linked care plan and clinician-facing platform, which were incorporated into a separate feasibility study of digitally enhanced integrated cancer care. RESULTS: The findings from the interview study demonstrated the usability, acceptability, and potential value of CHAT-P. Men recognized the benefits of a personalized approach and the importance of a holistic understanding of their needs. Preparation for the consultation by the completion of CHAT-P was also recognized as empowering. The possible limitations identified were related to the importance of care teams responding to the issues selected in the assessment. The subsequent feasibility study highlighted the need for attention to men's psychological concerns and demonstrated the ability of CHAT-P to capture red flag symptoms requiring urgent investigation. CONCLUSIONS: CHAT-P offers an innovative means by which men can communicate their concerns to their health care teams before a physical or remote consultation. There is now a need for a full evaluation of the implementation process and outcomes where CHAT-P is introduced into the clinical pathway. There is also scope for adapting the CHAT-P model to other cancers.

Atrial Myxoma Presenting as an Atypical Stroke in a Young Patient With a Recent COVID-19 Infection.

Atrial myxomas are the most common primary tumor of the heart and can occasionally present as an ischemic stroke with neurologic symptoms secondary to embolic phenomena. We present a case of a 42-year-old male with multiple cardiovascular risk factors and coronavirus disease 2019 (COVID-19) infection two months prior who presented to the emergency department with unilateral left-sided weakness and paresthesia. After being diagnosed with multifocal ischemic strokes, further evaluation utilizing a transesophageal echocardiogram (TEE) revealed a 5 × 2 cm left atrial myxoma prolapsing the mitral valve, which was the presumed cause of the patient's strokes. The myxoma was successfully removed via robotic thoracoscopy. Our case demonstrates the importance of considering atrial myxoma in the evaluation of stroke in young and middle-aged patients even in the presence of multiple cardiovascular and thrombotic risk factors.

A lightweight magnetically shielded room with active shielding.

Magnetically shielded rooms (MSRs) use multiple layers of materials such as MuMetal to screen external magnetic fields that would otherwise interfere with high precision magnetic field measurements such as magnetoencephalography (MEG). Optically pumped magnetometers (OPMs) have enabled the development of wearable MEG systems which have the potential to provide a motion tolerant functional brain imaging system with high spatiotemporal resolution. Despite significant promise, OPMs impose stringent magnetic shielding requirements, operating around a zero magnetic field resonance within a dynamic range of ± 5 nT. MSRs developed for OPM-MEG must therefore effectively shield external sources and provide a low remnant magnetic field inside the enclosure. Existing MSRs optimised for OPM-MEG are expensive, heavy, and difficult to site. Electromagnetic coils are used to further cancel the remnant field inside the MSR enabling participant movements during OPM-MEG, but present coil systems are challenging to engineer and occupy space in the MSR limiting participant movements and negatively impacting patient experience. Here we present a lightweight MSR design (30% reduction in weight and 40-60% reduction in external dimensions compared to a standard OPM-optimised MSR) which takes significant steps towards addressing these barriers. We also designed a 'window coil' active shielding system, featuring a series of simple rectangular coils placed directly onto the walls of the MSR. By mapping the remnant magnetic field inside the MSR, and the magnetic field produced by the coils, we can identify optimal coil currents and cancel the remnant magnetic field over the central cubic metre to just |B|= 670 ± 160 pT. These advances reduce the cost, installation time and siting restrictions of MSRs which will be essential for the widespread deployment of OPM-MEG.

On the techniques and standards of particulate matter sampling.

Air pollution and its limits are regulated by the environmental protection agency of an individual country according to their National Ambient Air Quality Standards (NAAQS). Particulate matter (e.g., TSP, PM10, and PM2.5) is one of the important criteria pollutants of NAAQS. Their measurement methods are specified in NAAQS, and detailed technical descriptions are given in standards. This review focuses on the sampling and analysis techniques and methods in the context of PM samplers' design mentioned in countries specific PM measuring standards (e.g., EPA Part 50, CEN 12341, IS 5182(23), etc.) and their comparison wherever is necessary. It discusses, different designs of PM samplers mentioned in standards and its important components, e.g., size fractionators cutoff efficiency, PM sampler head design, flow measurement, and calibration, and also addresses the important issues that are the limitation of present standards. Our review reveals that most of the country-specific standards show common practice in measuring PM2.5 using WINS impactor and VSCC cyclone as mentioned in EPA Part 50, except European Union (EU) standards, which has different design and parameters. For PM10 measurement, sampler design is different in EU and Indian standards than that of U.S. EPA and other countries' standards, which is discussed in length here. All standards lack in pointing some inherent problems like change in D50 cutoff of size fractionator of sampler under a high particle mass loading condition, which is common in countries like China and India. Other important issues where most of the standards lack include PM head design and specification, a key component of PM sampler on which the mass measurement results are largely dependent.Implications: The review paper discusses the air quality standards compliances of different countries and their comparisons. It focuses on the sampling and analysis techniques in context of PM samplers' design mentioned in countries specific PM measuring standards, and also addresses the important issues that are not mentioned in standards. Therefore, the discussions and findings of the review may be very useful while revising the existing air quality standards of different countries and to fill the research gap in this domain. Further, we have discussed several technical issues described in standards related to PM sampling which may be very helpful for PM sampler designing or modification in current designs as per the prevailing ambient conditions of a country.

Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factors.

BACKGROUND : Data are limited regarding pancreatic cancer diagnosed following a pancreaticobiliary endoscopic ultrasound (EUS) that does not diagnose pancreatic cancer. We have studied the frequency of, and factors associated with, post-EUS pancreatic cancer (PEPC) and 1-year mortality. METHODS : Between 2010 and 2017, patients with pancreatic cancer and a preceding pancreaticobiliary EUS were identified in a national cohort using Hospital Episode Statistics. Patients with a pancreaticobiliary EUS 6-18 months before a later pancreatic cancer diagnosis were the PEPC cases; controls were those with pancreatic cancer diagnosed within 6 months of pancreaticobiliary EUS. Multivariable logistic regression models examined the factors associated with PEPC and a Cox regression model examined factors associated with 1-year cumulative mortality. RESULTS : 9363 pancreatic cancer patients were studied; 93.5 % identified as controls (men 53.2 %; median age 68 [interquartile range (IQR) 61-75]); 6.5 % as PEPC cases (men 58.2 %; median age 69 [IQR 61-77]). PEPC was associated with older age (≥ 75 years compared with < 65 years, odds ratio [OR] 1.42, 95 %CI 1.15-1.76), increasing co-morbidity (Charlson co-morbidity score > 5, OR 1.90, 95 %CI 1.49-2.43), chronic pancreatitis (OR 3.13, 95 %CI 2.50-3.92), and diabetes mellitus (OR 1.58, 95 %CI 1.31-1.90). Metal biliary stents (OR 0.57, 95 %CI 0.38-0.86) and EUS-FNA (OR 0.49, 95 %CI 0.41-0.58) were inversely associated with PEPC. PEPC was associated with a higher cumulative mortality at 1 year (hazard ratio 1.12, 95 %CI 1.02-1.24), with only 14 % of PEPC patients (95 %CI 12 %-17 %) having a surgical resection, compared with 21 % (95 %CI 20 %-22 %) of controls. CONCLUSIONS : PEPC occurred in 6.5 % of patients and was associated with chronic pancreatitis, older age, more co-morbidities, and specifically diabetes mellitus. PEPC was associated with a worse prognosis and lower surgical resection rates.

A Phase 2 Randomized, Double-Blind, Placebo-controlled Trial of Oral Camostat Mesylate for Early Treatment of COVID-19 Outpatients Showed Shorter Illness Course and Attenuation of Loss of Smell and Taste.

Importance: Early treatment of mild SARS-CoV-2 infection might lower the risk of clinical deterioration in COVID-19. Objective: To determine whether oral camostat mesylate would reduce upper respiratory SARS-CoV-2 viral load in newly diagnosed outpatients with mild COVID-19, and would lead to improvement in COVID-19 symptoms. Design: From June, 2020 to April, 2021, we conducted a randomized, double-blind, placebo-controlled phase 2 trial. Setting: Single site, academic medical center, outpatient setting in Connecticut, USA. Participants: Of 568 COVID-19 positive potential adult participants diagnosed within 3 days of study entry and assessed for eligibility, 70 were randomized and 498 were excluded (198 did not meet eligibility criteria, 37 were not interested, 265 were excluded for unknown or other reasons). The primary inclusion criteria were a positive SARS-CoV-2 nucleic acid amplification result in adults within 3 days of screening regardless of COVID-19 symptoms. Intervention: Treatment was 7 days of oral camostat mesylate, 200 mg po four times a day, or placebo. Main Outcomes and Measures: The primary outcome was reduction of 4-day log10 nasopharyngeal swab viral load by 0.5 log10 compared to placebo. The main prespecified secondary outcome was reduction in symptom scores as measured by a quantitative Likert scale instrument, Flu-PRO-Plus modified to measure changes in smell/taste measured using FLU-PRO-Plus. Results: Participants receiving camostat had statistically significant lower quantitative symptom scores (FLU-Pro-Plus) at day 6, accelerated overall symptom resolution and notably improved taste/smell, and fatigue beginning at onset of intervention in the camostat mesylate group compared to placebo. Intention-to-treat analysis demonstrated that camostat mesylate was not associated with a reduction in 4-day log10 NP viral load compared to placebo. Conclusions and relevance: The camostat group had more rapid resolution of COVID-19 symptoms and amelioration of the loss of taste and smell. Camostat compared to placebo was not associated with reduction in nasopharyngeal SARS-COV-2 viral load. Additional clinical trials are warranted to validate the role of camostat mesylate on SARS-CoV-2 infection in the treatment of mild COVID-19. Trial registration: Clinicaltrials.gov, NCT04353284 (04/20/20)(https://clinicaltrials.gov/ct2/show/NCT04353284?term=camostat+%2C+yale&draw=2&rank=1).