Diagnosis and treatment of chlamydia and gonorrhoea in general practice in England 2000–2011: a population-based study using data from the UK Clinical Practice Research Datalink

Objectives: To determine the relative contribution of general practices (GPs) to the diagnosis of chlamydia and gonorrhoea in England and whether treatment complied with national guidelines. Design: Analysis of longitudinal electronic health records in the Clinical Practice Research Datalink (CPRD) and national sexually transmitted infection (STI) surveillance databases, England, 2000–2011. Setting: GPs, and community and specialist STI services. Participants: Patients diagnosed with chlamydia (n=1 386 169) and gonorrhoea (n=232 720) at CPRD GPs, and community and specialist STI Services from 2000–2011. Main outcome measures: Numbers and rates of chlamydia and gonorrhoea diagnoses; percentages of patients diagnosed by GPs relative to other services; percentage of GP patients treated and antimicrobials used; percentage of GP patients referred. Results: The diagnosis rate (95% CI) per 100 000 population of chlamydia in GP increased from 22.8 (22.4–23.2) in 2000 to 29.3 (28.8–29.7) in 2011 (p<0.001), while the proportion treated increased from 59.5% to 78.4% (p=0.001). Over 90% were prescribed a recommended antimicrobial. Over the same period, the diagnosis rate (95% CI) per 100 000 population of gonorrhoea in GP ranged between 3.2 (3–3.3) and 2.4 (2.2–2.5; p=0.607), and the proportion treated ranged between 32.7% and 53.6% (p=0.262). Despite being discontinued as a recommended therapy for gonorrhoea in 2005, ciprofloxacin accounted for 42% of prescriptions in 2007 and 20% in 2011. Over the study period, GPs diagnosed between 9% and 16% of chlamydia cases and between 6% and 9% of gonorrhoea cases in England. Conclusions: GP makes an important contribution to the diagnosis and treatment of bacterial STIs in England. While most patients diagnosed with chlamydia were managed appropriately, many of those treated for gonorrhoea received antimicrobials no longer recommended for use. Given the global threat of antimicrobial resistance, GPs should remain abreast of national treatment guidelines and alert to treatment failure in their patients

Emergency surgery admissions and the COVID-19 pandemic: did the first wave really change our practice? Results of an ACOI/WSES international retrospective cohort audit on 6263 patients

Introduction The COVID-19 pandemic is having a deep impact on emergency surgical services, with a significant reduction of patients admitted into emergency surgical units world widely. Reliable figures of this reduction have not been produced yet. Our international audit aimed at giving a precise snapshot of the absolute and relative changes of emergency surgical admissions at the outbreak of the pandemic. Materials and methods Datasets of patients admitted as general surgical emergencies into 45 internationally distributed emergency surgical units during the months of March and April 2020 (Covid-19 pandemic outbreak) were collected and compared with those of patients admitted into the same units during the months of March and April 2019 (pre-Covid-19). Primary endpoint was to evaluate the relative variation of the presentation symptoms and discharge diagnoses between the two study periods. Secondary endpoint was to identify the possible change of therapeutic strategy during the same two periods. Results Forty-five centres participated sent their anonymised data to the study hub, for a total of 6263 patients. Of these, 3810 were admitted in the pre-Covid period and 2453 in the Covid period, for a 35.6% absolute reduction. The most common presentation was abdominal pain, whose incidence did not change between the two periods, but in the Covid period patients presented less frequently with anal pain, hernias, anaemia and weight loss. ASA 1 and low frailty patients were admitted less frequently, while ASA&gt;1 and frail patients showed a relative increase. The type of surgical access did not change significantly, but lap-to-open conversion rate halved between the two study periods. Discharge diagnoses of appendicitis and diverticulitis reduced significantly, while bowel ischaemia and perianal ailments had a significant relative increase. Conclusions Our audit demonstrates a significant overall reduction of emergency surgery admissions at the outbreak of the Covid-19 pandemic with a minimal change of the proportions of single presentations, diagnoses and treatments. These findings may open the door to new ways of managing surgical emergencies without engulfing the already busy hospitals

The weekend effect on the provision of Emergency Surgery before and during the COVID-19 pandemic: case-control analysis of a retrospective multicentre database

Introduction The concept of "weekend effect", that is, substandard healthcare during weekends, has never been fully demonstrated, and the different outcomes of emergency surgical patients admitted during weekends may be due to different conditions at admission and/or different therapeutic approaches. Aim of this international audit was to identify any change of pattern of emergency surgical admissions and treatments during weekends. Furthermore, we aimed at investigating the impact of the COVID-19 pandemic on the alleged "weekend effect". Methods The database of the CovidICE-International Study was interrogated, and 6263 patients were selected for analysis. Non-trauma, 18+ yo patients admitted to 45 emergency surgery units in Europe in the months of March-April 2019 and March-April 2020 were included. Demographic and clinical data were anonymised by the referring centre and centrally collected and analysed with a statistical package. This study was endorsed by the Association of Italian Hospital Surgeons (ACOI) and the World Society of Emergency Surgery (WSES). Results Three-quarters of patients have been admitted during workdays and only 25.7% during weekends. There was no difference in the distribution of gender, age, ASA class and diagnosis during weekends with respect to workdays. The first wave of the COVID pandemic caused a one-third reduction of emergency surgical admission both during workdays and weekends but did not change the relation between workdays and weekends. The treatment was more often surgical for patients admitted during weekends, with no difference between 2019 and 2020, and procedures were more often performed by open surgery. However, patients admitted during weekends had a threefold increased risk of laparoscopy-to-laparotomy conversion (1% vs. 3.4%). Hospital stay was longer in patients admitted during weekends, but those patients had a lower risk of readmission. There was no difference of the rate of rescue surgery between weekends and workdays. Subgroup analysis revealed that interventional procedures for hot gallbladder were less frequently performed on patients admitted during weekends. Conclusions Our analysis revealed that demographic and clinical profiles of patients admitted during weekends do not differ significantly from workdays, but the therapeutic strategy may be different probably due to lack of availability of services and skillsets during weekends. The first wave of the COVID-19 pandemic did not impact on this difference

DNA topoisomerases participate in fragility of the oncogene RET

Fragile site breakage was previously shown to result in rearrangement of the RET oncogene, resembling the rearrangements found in thyroid cancer. Common fragile sites are specific regions of the genome with a high susceptibility to DNA breakage under conditions that partially inhibit DNA replication, and often coincide with genes deleted, amplified, or rearranged in cancer. While a substantial amount of work has been performed investigating DNA repair and cell cycle checkpoint proteins vital for maintaining stability at fragile sites, little is known about the initial events leading to DNA breakage at these sites. The purpose of this study was to investigate these initial events through the detection of aphidicolin (APH)-induced DNA breakage within the RET oncogene, in which 144 APHinduced DNA breakpoints were mapped on the nucleotide level in human thyroid cells within intron 11 of RET, the breakpoint cluster region found in patients. These breakpoints were located at or near DNA topoisomerase I and/or II predicted cleavage sites, as well as at DNA secondary structural features recognized and preferentially cleaved by DNA topoisomerases I and II. Co-treatment of thyroid cells with APH and the topoisomerase catalytic inhibitors, betulinic acid and merbarone, significantly decreased APH-induced fragile site breakage within RET intron 11 and within the common fragile site FRA3B. These data demonstrate that DNA topoisomerases I and II are involved in initiating APH-induced common fragile site breakage at RET, and may engage the recognition of DNA secondary structures formed during perturbed DNA replication

The Sigma - D relation for planetary nebulae

We present an extended analysis of the relation between radio surface brightness and diameter -- the so-called $\Sigma-D$ relation for planetary nebulae (PNe). We revise our previous derivation of the theoretical $\Sigma-D$ relation for the evolution of bremsstrahlung surface brightness in order to include the influence of the fast wind from the central star. Different theoretical forms are derived: $\Sigma \propto D^{-1}$ for the first and second phases of evolution and $\Sigma\propto D^{-3}$ for the final stage of evolution. Also, we analyzed several different Galactic PN samples. All samples are influenced by severe selection effects, but Malmquist bias seems to be less influential here than in the supernova remnant (SNR) samples. We derived empirical $\Sigma-D$ relations for 27 sample sets using 6 updated PN papers from which an additional 21 new sets were extracted. Twenty four of these have a trivial form of $\beta \approx 2$. However, we obtain one empirical $\Sigma-D$ relation that may be useful for determining distances to PNe. This relation is obtained by extracting a recent nearby (< 1 kpc) Galactic PN sample.Comment: 12 pages, 3 tables, 4 figures. Accepted for publication in Astronomy & Astrophysic

Identification of a large rearrangement in CYLD as a cause of familial cylindromatosis

Pathogenic mutations in CYLD can be identified in patients affected with Brooke-Spiegler syndrome, (Familial) Cylindromatosis or multiple familial trichoepithelioma. To date, only technologies which are able to identify small point mutations in CYLD, such as sequence and WAVE analysis, were used. Here we describe the identification of a larger rearrangement identified by Quantitative PCR analysis of CYLD, indicating that a combination of these technologies is necessary when searching for pathogenic mutations in CYLD

COSMIC 2005

The Catalogue Of Somatic Mutations In Cancer (COSMIC) database and web site was developed to preserve somatic mutation data and share it with the community. Over the past 25 years, approximately 350 cancer genes have been identified, of which 311 are somatically mutated. COSMIC has been expanded and now holds data previously reported in the scientific literature for 28 known cancer genes. In addition, there is data from the systematic sequencing of 518 protein kinase genes. The total gene count in COSMIC stands at 538; 25 have a mutation frequency above 5% in one or more tumour type, no mutations were found in 333 genes and 180 are rarely mutated with frequencies <5% in any tumour set. The COSMIC web site has been expanded to give more views and summaries of the data and provide faster query routes and downloads. In addition, there is a new section describing mutations found through a screen of known cancer genes in 728 cancer cell lines including the NCI-60 set of cancer cell lines

Improved precision on the experimental E0 decay branching ratio of the Hoyle state

Stellar carbon synthesis occurs exclusively via the $3\alpha$ process, in which three $\alpha$ particles fuse to form $^{12}$C in the excited Hoyle state, followed by electromagnetic decay to the ground state. The Hoyle state is above the $\alpha$ threshold, and the rate of stellar carbon production depends on the radiative width of this state. The radiative width cannot be measured directly, and must instead be deduced by combining three separately measured quantities. One of these quantities is the $E0$ decay branching ratio of the Hoyle state, and the current $10$\% uncertainty on the radiative width stems mainly from the uncertainty on this ratio. The $E0$ branching ratio was deduced from a series of pair conversion measurements of the $E0$ and $E2$ transitions depopulating the $0^+_2$ Hoyle state and $2^+_1$ state in $^{12}$C, respectively. The excited states were populated by the $^{12}$C$(p,p^\prime)$ reaction at 10.5 MeV beam energy, and the pairs were detected with the electron-positron pair spectrometer, Super-e, at the Australian National University. The deduced branching ratio required knowledge of the proton population of the two states, as well as the alignment of the $2^+_1$ state in the reaction. For this purpose, proton scattering and $\gamma$-ray angular distribution experiments were also performed. An $E0$ branching ratio of $\Gamma^{E0}_{\pi}/\Gamma=8.2(5)\times10^{-6}$ was deduced in the current work, and an adopted value of $\Gamma^{E0}_{\pi}/\Gamma=7.6(4)\times10^{-6}$ is recommended based on a weighted average of previous literature values and the new result. The new recommended value for the $E0$ branching ratio is about 14% larger than the previous adopted value of $\Gamma^{E0}_{\pi}/\Gamma=6.7(6)\times10^{-6}$, while the uncertainty has been reduced from 9% to 5%.Comment: Accepted for publication as a Regular Article in Phys. Rev. C on July 29 202

New searches for HI 21-cm in damped Lyman-alpha absorption systems

We present the results of three separate searches for HI 21-cm absorption in a total of twelve damped Lyman-alpha absorption systems (DLAs) and sub-DLAs over the redshift range z = 0.86-3.37. We find no absorption in the five systems for which we obtain reasonable sensitivities and add the results to those of other recent surveys in order to investigate factors which could have an effect on the detection rate: We provide evidence that the mix of spin temperature/covering factor ratios seen at low redshift may also exist at high redshift, with a correlation between the 21-cm line strength and the total neutral hydrogen column density, indicating a roughly constant spin temperature/covering factor ratio for all of the DLAs searched. Also, by considering the geometry of a flat expanding Universe together with the projected sizes of the background radio emission regions, we find, for the detections, that the 21-cm line strength is correlated with the size of the absorber. For the non-detections it is apparent that larger absorbers (covering factors) are required in order to exhibit 21-cm absorption, particularly if these DLAs do not arise in spiral galaxies. We also suggest that the recent z = 2.3 detection towards TXS 0311+430 arises in a spiral galaxy, but on the basis of a large absorption cross-section and high metallicity, rather than a low spin temperatureComment: 11 pages, accepted by MNRA

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein–protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation