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IMPORTANCE: Whether the severity and mortality of COVID-19 in patients with cancer have improved in terms of disease management and capacity is yet to be defined. OBJECTIVE: To test whether severity and mortality from COVID-19 among patients with cancer have improved during the course of the pandemic. DESIGN, SETTING, AND PARTICIPANTS: OnCovid is a European registry that collects data on consecutive patients with solid or hematologic cancer and COVID-19. This multicenter case series study included real-world data from 35 institutions across 6 countries (UK, Italy, Spain, France, Belgium, and Germany). This update included patients diagnosed between February 27, 2020, and February, 14, 2021. Inclusion criteria were confirmed diagnosis of SARS-CoV-2 infection and a history of solid or hematologic cancer. EXPOSURES: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: Deaths were differentiated at 14 days and 3 months as the 2 landmark end points. Patient characteristics and outcomes were compared by stratifying patients across 5 phases (February to March 2020, April to June 2020, July to September 2020, October to December 2020, and January to February 2021) and across 2 major outbreaks (February to June 2020 and July 2020 to February 2021). RESULTS: At data cutoff, 2795 consecutive patients were included, with 2634 patients eligible for analysis (median [IQR] age, 68 [18-77] years ; 52.8% men). Eligible patients demonstrated significant time-dependent improvement in 14-day case-fatality rate (CFR) with estimates of 29.8% (95% CI, 0.26-0.33) for February to March 2020; 20.3% (95% CI, 0.17-0.23) for April to June 2020; 12.5% (95% CI, 0.06-22.90) for July to September 2020; 17.2% (95% CI, 0.15-0.21) for October to December 2020; and 14.5% (95% CI, 0.09-0.21) for January to February 2021 (all P < .001) across the predefined phases. Compared with the second major outbreak, patients diagnosed in the first outbreak were more likely to be 65 years or older (974 of 1626 [60.3%] vs 564 of 1008 [56.1%]; P = .03), have at least 2 comorbidities (793 of 1626 [48.8%] vs 427 of 1008 [42.4%]; P = .001), and have advanced tumors (708 of 1626 [46.4%] vs 536 of 1008 [56.1%]; P < .001). Complications of COVID-19 were more likely to be seen (738 of 1626 [45.4%] vs 342 of 1008 [33.9%]; P < .001) and require hospitalization (969 of 1626 [59.8%] vs 418 of 1008 [42.1%]; P < .001) and anti–COVID-19 therapy (1004 of 1626 [61.7%] vs 501 of 1008 [49.7%]; P < .001) during the first major outbreak. The 14-day CFRs for the first and second major outbreaks were 25.6% (95% CI, 0.23-0.28) vs 16.2% (95% CI, 0.13-0.19; P < .001), respectively. After adjusting for country, sex, age, comorbidities, tumor stage and status, anti–COVID-19 and anticancer therapy, and COVID-19 complications, patients diagnosed in the first outbreak had an increased risk of death at 14 days (hazard ratio [HR], 1.85; 95% CI, 1.47-2.32) and 3 months (HR, 1.28; 95% CI, 1.08-1.51) compared with those diagnosed in the second outbreak. CONCLUSIONS AND RELEVANCE: The findings of this registry-based study suggest that mortality in patients with cancer diagnosed with COVID-19 has improved in Europe; this improvement may be associated with earlier diagnosis, improved management, and dynamic changes in community transmission over time.

ABSTRACTThis article argues that Coventry’s house of correction did not follow the general tendency for such institutions by becoming a mere lock-up, but instead formed a long-lasting part of the corporation’s attempts to strengthen the city’s social fabric. Despite several crises as successive masters fell out of favour, it remained one of a small minority of urban bridewells able to set prisoners to work, whilst also developing a range of relief roles: providing work for the destitute, temporary refuge for vulnerable children and adults, and later pre-apprenticeship training for boys from the hospital school. The size of its premises, the corporation’s use of alternative punishments to spread the penal load, and the rigorous measures taken to exclude strangers, contributed to the bridewell’s ability to maintain its range of provision for the city.

Oncolytic virotherapies (OV) based on human adenoviral (HAdV) vectors hold significant promise for the treatment of advanced ovarian cancers where local, intraperitoneal delivery to tumour metastases is feasible, bypassing many complexities associated with intravascular delivery. The efficacy of HAdV-C5-based OV is hampered by a lack of tumour selectivity, where the primary receptor, hCAR, is commonly downregulated during malignant transformation. Conversely, folate receptor alpha (FRα) is highly expressed on ovarian cancer cells, providing a compelling target for tumour selective delivery of virotherapies. Here, we identify high-affinity FRα-binding oligopeptides for genetic incorporation into HAdV-C5 vectors. Biopanning identified a 12-mer linear peptide, DWSSWVYRDPQT, and two 7-mer cysteine-constrained peptides, CIGNSNTLC and CTVRTSAEC that bound FRα in the context of the phage particle. Synthesised lead peptide, CTVRTSAEC, bound specifically to FRα and could be competitively inhibited with folic acid. To assess the capacity of the elucidated FRα-binding oligopeptides to target OV to FRα, we genetically incorporated the peptides into the HAdV-C5 fiber-knob HI loop including in vectors genetically ablated for hCAR interactions. Unfortunately, the recombinant vectors failed to efficiently target transduction via FRα due to defective intracellular trafficking following entry via FRα, indicating that whilst the peptides identified may have potential for applications for targeted drug delivery, they require additional refinement for targeted virotherapy applications.

Urothelial carcinomas of the upper urinary tract (UTUCs) are rare, with poorer stage-for-stage prognosis than urothelial carcinomas of the urinary bladder. No international consensus exists on the benefit of adjuvant chemotherapy for patients with UTUCs after nephroureterectomy with curative intent. The POUT (Peri-Operative chemotherapy versus sUrveillance in upper Tract urothelial cancer) trial aimed to assess the efficacy of systemic platinum-based chemotherapy in patients with UTUCs.

Human papillomavirus (HPV) infection in cases of squamous cell carcinoma of the oropharynx is a powerful predictive and prognostic biomarker. We describe how the use of next-generation sequencing can provide a novel method for the detection of HPV in DNA isolated from formalin-fixed paraffin-embedded tissues. Using this methodology in a cohort of 44 head and neck tumors, we identified the samples that contained HPV sequences, the viral subtype involved, and a direct readout of viral load. Specificity of HPV detection by sequencing compared to traditional detection methods using either PCR or p16 immunohistochemistry was 100%. Sensitivity was 50% when either compared to PCR [confidence interval (CI) = 29% to 71%] or 75% when compared to p16 (CI = 47% to 91%). In addition, we demonstrate the ability of next-generation sequencing to detect other HPV subtypes that would not have been detected by traditional methods, and we demonstrated the ability to apply this method to any tumor and any virus in a panel of eight human cancer cell lines. This methodology also provides a tumor genomic copy number karyogram, and in the samples analyzed here, a lower level of chromosome instability was detected in HPV-positive tumors compared to HPV-negative tumors, as observed in previous studies. Thus, the use of next-generation sequencing for the detection of HPV provides a multiplicity of data with clinical significance in a single test.

The potassium permanganate treatment of certain diseases of toxic and infectious origin first came to my attention in a purely accidental manner. A professional colleague inadvertently mentioned that this oxidizing antiseptic and deodorant, held in aqueous solution and slowly injected into the rectum as a retained enema, had been reported from England as productive of startling results in pneumonia. I do not know that I gave much heed to the reported discovery at the time, if such a discovery there was. Like most practitioners I had become somewhat immune to enthusiasm over 'discoveries' of pneumonia specifics. Too many of them

The augmenting effect of chronic inflammation on bladder cancer was studied in female Swiss mice treated with N-[4-(5-nitro-2-furyl)-2-thiazolyl] formamide (FANFT), 0.15% by weight of diet for 20 weeks. To produce chronic inflammation one silk suture and one catgut suture were placed through the bladder wall of 63 mice to receive FANFT and 18 to receive normal diet. In remaining mice (no. = 62) the bladder was simply touched without suture insertion. Thirty-two animals treated with FANFT and 33 treated with FANFT + sutures also received supplements to their drinking water throughout the experiment of the sulfhydryl-reducing agent N-acetylcysteine (500mg./kg. body weight/day). Seven weeks following FANFT treatment, bladder cancers developed in 12% of mice with sutures and FANFT and in 19% of those with sutures, FANFT, and N-acetylcysteine. No cancers developed in mice receiving FANFT alone or FANFT with N-acetylcysteine and none in mice treated with sutures only. Placement of silk sutures through the bladder wall of mice augments FANFT-induced bladder cancer. N-acetylcysteine at these doses does not influence the incidence.

Abstract: The availability of an endoscopic support brace for use during gastrointestinal endoscopy is described.

The analgesic efficacy of locally injected bupivacaine was studied in 40 patients undergoing hemorrhoidectomy. After a standard Milligan-Morgan hemorrhoidectomy, 40 age- and sex-matched patients were randomized to receive either 0.5 percent bupivacaine (1.5 mg/kg) in adrenaline solution (1∶200,000) injected into the perianal area, or equivalent volumes of adrenaline solution. Intramuscular opiate was available on demand during the postoperative period, and the amount and timing of analgesia given was recorded. All patients noted their pain on a daily basis using a linear analogue scale, and all patients answered a questionnaire assessing analgesic efficacy. Although the median time interval between surgery and first analgesic demand was nearly four times greater for patients receiving bupivacaine compared with adrenaline solution, there was no difference in the levels of pain recorded or in the overall opiate requirements. Local injection of bupivacaine after hemorrhoidectomy provides initial pain relief, but patients do not obtain an overall analgesic benefit.

The Scottish Wildlife Trust is one of three partners in the Isle of Eigg Heritage Trust. Community ownership has given it the green light to start essential work to reverse ecological degradation and to increase biodiversity. [ABSTRACT FROM AUTHOR]

The Critical Sea Test (CST) is an empirical Navy program which collects low‐frequency (100–1000 Hz) environmental acoustics measurements in order to provide a diverse, high‐quality database for sonar performance prediction. During the course of its experiments in direct path bottom reverberation, CST has observed frequency, grazing angle, and waveform behaviors which differ significantly from those assumed in commonly available bottomscattering strength models. For empirical programs, deviations from standard models are significant because they limit the ability to extrapolate survey measurements into sonar performance scenarios. The most controversial aspect of the coherent source experiments has been the observation of a pulse length dependence in the scattering strength measurements beyond the linear term normally associated with ensonified area. This paper discusses CST’s bottomscattering strength measurement technique and summarizes the pulse length ‘‘anomaly’’ results for a variety of geographic areas. Because these results run counter to standard modeling assumptions, this paper will also discuss the data quality procedures used to reach these conclusions. [Work supported by SPAWAR.]

A comprehensive low‐frequency (<1000‐Hz) low grazing angle (<30°) sea surface acoustic scatter experiment was conducted during February/March 1992 in the Gulf of Alaska. During data collection, wind speeds ranged from 3–17.5 m/s and sea states from 2–6. cw waveforms less than 500 ms in length at 250, 380, 900, and 935 Hz were transmitted by three collinear vertical towed source arrays. Surface scattered energy was received in 17 cosine‐spaced beams by a horizontal source‐ship‐towed line array. This experimental geometry allowed measurement of surface scattering strength as a function of mean grazing angle, frequency, and horizontal bistatic angle. Analysis of these measurements in terms of these dependencies is presented along with comparison to current surface scattering strength model predictions.

The derivation of scattering strengths from acoustic field data involves applying the active sonar equation to the measured reverberation response. However, due to the typical nonstationarity observed in the direct‐path reverberation time series (e.g., 10 dB/s), the choice of appropriate corresponding grazing angles becomes more problematical as the duration of the transmitted signal increases. Direct‐path measurements of low‐frequency (200–1000 Hz) acoustic surface scattering were made in the Gulf of Alaska in the February of 1992 using interleaved SUS and pulsed waveforms (cw, FM). Backscattering strengths were derived for pulse lengths varying between 50 ms and 2.4 s. A comparison of results revealed that scattering strengths have a nontrivial dependence on signal type and pulse length, and on the signal‐processing methodology used in their derivation. General implications for deriving scattering strengths from nonstationary time‐series data will be discussed. [Work supported by ONR (NRL).]

The Ty transposable elements of Saccharomyces cerevisiae form a heterogeneous family within which two broad structural classes (I and II) exist. The two classes differ by two large substitutions and many restriction sites. We show that, like class I elements a class II element, Tyl-17, also appears to contain at least two major protein coding regions, designated TYA and TYB, and the organisational relationship of these regions has been conserved. The TYA genes of both classes encode proteins, designated pl proteins, with an approximate molecular weight of 5Ø Kd and, despite considerable variation between the TYA regions at the DNA level, the structures of these proteins are remarkably similar. These observations strongly suggest that the pl proteins of Ty elements are functionally significant and that they have been subject to selection

During February/March 1992 a comprehensive low‐frequency (<1000 Hz) and low‐grazing angle (<30 deg) acoustic sea surface scatter and air/sea interaction experiment was conducted in the Gulf of Alaska. For comparison with acoustic models, measurements were made of air/sea boundary descriptions such as near‐surface bubble characteristics, wind speed, wave height, whitecap coverage, volume scatterers (fish), wind stress, etc. A variety of waveforms of short duration (<500 ms) were scattered from a surface path simultaneously isonified by three collinear vertical towed source arrays at frequencies around 250, 400, and 1000 Hz. Surface‐scattered energy was received on a horizontal line array towed by the source ship. During the measurement wind speeds from 4 to 19 m/s and rms wave heights from 0.9 to 2.3 m occurred associated with sea states 2 to 6. Surface grazing angles of 4 to 32 deg and horizontal bistatic angles of 15 to 82 deg were observed. Scattering strength analysis includes frequency, grazing angle, waveform, and wind speed dependence as well as correlation with air/sea boundary descriptors. Current scattering strength model predictions utilizing the appropriate measured environmental parameters will be compared to measured data.