Reducing the transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a global priority. Contact tracing identifies people who were recently in contact with an infected ...individual, in order to isolate them and reduce further transmission. Digital technology could be implemented to augment and accelerate manual contact tracing. Digital tools for contact tracing may be grouped into three areas: 1) outbreak response; 2) proximity tracing; and 3) symptom tracking. We conducted a rapid review on the effectiveness of digital solutions to contact tracing during infectious disease outbreaks.
To assess the benefits, harms, and acceptability of personal digital contact tracing solutions for identifying contacts of an identified positive case of an infectious disease.
An information specialist searched the literature from 1 January 2000 to 5 May 2020 in CENTRAL, MEDLINE, and Embase. Additionally, we screened the Cochrane COVID-19 Study Register.
We included randomised controlled trials (RCTs), cluster-RCTs, quasi-RCTs, cohort studies, cross-sectional studies and modelling studies, in general populations. We preferentially included studies of contact tracing during infectious disease outbreaks (including COVID-19, Ebola, tuberculosis, severe acute respiratory syndrome virus, and Middle East respiratory syndrome) as direct evidence, but considered comparative studies of contact tracing outside an outbreak as indirect evidence. The digital solutions varied but typically included software (or firmware) for users to install on their devices or to be uploaded to devices provided by governments or third parties. Control measures included traditional or manual contact tracing, self-reported diaries and surveys, interviews, other standard methods for determining close contacts, and other technologies compared to digital solutions (e.g. electronic medical records).
Two review authors independently screened records and all potentially relevant full-text publications. One review author extracted data for 50% of the included studies, another extracted data for the remaining 50%; the second review author checked all the extracted data. One review author assessed quality of included studies and a second checked the assessments. Our outcomes were identification of secondary cases and close contacts, time to complete contact tracing, acceptability and accessibility issues, privacy and safety concerns, and any other ethical issue identified. Though modelling studies will predict estimates of the effects of different contact tracing solutions on outcomes of interest, cohort studies provide empirically measured estimates of the effects of different contact tracing solutions on outcomes of interest. We used GRADE-CERQual to describe certainty of evidence from qualitative data and GRADE for modelling and cohort studies.
We identified six cohort studies reporting quantitative data and six modelling studies reporting simulations of digital solutions for contact tracing. Two cohort studies also provided qualitative data. Three cohort studies looked at contact tracing during an outbreak, whilst three emulated an outbreak in non-outbreak settings (schools). Of the six modelling studies, four evaluated digital solutions for contact tracing in simulated COVID-19 scenarios, while two simulated close contacts in non-specific outbreak settings. Modelling studies Two modelling studies provided low-certainty evidence of a reduction in secondary cases using digital contact tracing (measured as average number of secondary cases per index case - effective reproductive number (R
)). One study estimated an 18% reduction in R
with digital contact tracing compared to self-isolation alone, and a 35% reduction with manual contact-tracing. Another found a reduction in R
for digital contact tracing compared to self-isolation alone (26% reduction) and a reduction in R
for manual contact tracing compared to self-isolation alone (53% reduction). However, the certainty of evidence was reduced by unclear specifications of their models, and assumptions about the effectiveness of manual contact tracing (assumed 95% to 100% of contacts traced), and the proportion of the population who would have the app (53%). Cohort studies Two cohort studies provided very low-certainty evidence of a benefit of digital over manual contact tracing. During an Ebola outbreak, contact tracers using an app found twice as many close contacts per case on average than those using paper forms. Similarly, after a pertussis outbreak in a US hospital, researchers found that radio-frequency identification identified 45 close contacts but searches of electronic medical records found 13. The certainty of evidence was reduced by concerns about imprecision, and serious risk of bias due to the inability of contact tracing study designs to identify the true number of close contacts. One cohort study provided very low-certainty evidence that an app could reduce the time to complete a set of close contacts. The certainty of evidence for this outcome was affected by imprecision and serious risk of bias. Contact tracing teams reported that digital data entry and management systems were faster to use than paper systems and possibly less prone to data loss. Two studies from lower- or middle-income countries, reported that contact tracing teams found digital systems simpler to use and generally preferred them over paper systems; they saved personnel time, reportedly improved accuracy with large data sets, and were easier to transport compared with paper forms. However, personnel faced increased costs and internet access problems with digital compared to paper systems. Devices in the cohort studies appeared to have privacy from contacts regarding the exposed or diagnosed users. However, there were risks of privacy breaches from snoopers if linkage attacks occurred, particularly for wearable devices.
The effectiveness of digital solutions is largely unproven as there are very few published data in real-world outbreak settings. Modelling studies provide low-certainty evidence of a reduction in secondary cases if digital contact tracing is used together with other public health measures such as self-isolation. Cohort studies provide very low-certainty evidence that digital contact tracing may produce more reliable counts of contacts and reduce time to complete contact tracing. Digital solutions may have equity implications for at-risk populations with poor internet access and poor access to digital technology. Stronger primary research on the effectiveness of contact tracing technologies is needed, including research into use of digital solutions in conjunction with manual systems, as digital solutions are unlikely to be used alone in real-world settings. Future studies should consider access to and acceptability of digital solutions, and the resultant impact on equity. Studies should also make acceptability and uptake a primary research question, as privacy concerns can prevent uptake and effectiveness of these technologies.
Objectives
To assess the complications of transrectal (TR) compared to transperineal prostate (TP) biopsies.
Patients and Methods
Men diagnosed with prostate cancer between 1 April 2014 and 31 March ...2017 in England were identified in the National Prostate Cancer Audit. Administrative hospital data were then used to categorize the type of prostate biopsy and subsequent complications requiring hospital admission. Administrative hospital data were used to identify patients staying overnight immediately after biopsy and those readmitted separately for hospital admissions because of sepsis, urinary retention or haematuria. Procedure‐related mortality and total length of hospital stay within 30 days were also recorded. Generalized linear models were used to calculate adjusted risk differences (aRDs).
Results
A total of 73 630 patients undergoing prostate biopsy were identified. Those undergoing TP biopsy (n = 13 723) were more likely to have an overnight hospital stay (12.3% vs 2.4%; aRD 9.7%, 95% confidence interval CI 7.1–12.3), were less likely to be readmitted because of sepsis (1.0% vs 1.4%; aRD −0.4%, CI −0.6 to −0.2), and were more likely to be readmitted with urinary retention (1.9% vs 1.0%; aRD 1.1%, CI 0.7–1.4) than those undergoing a TR biopsy (n = 59 907). There were no significant differences in the risk of haematuria or mortality.
Conclusions
Our results showed that TP biopsy had a lower risk of readmission for sepsis but a higher risk of readmission for urinary retention than TR biopsy. Use of the TP route would prevent one readmission for sepsis in 278 patients at the cost of three additional patients readmitted for urinary retention.
Metasurfaces based on resonant nanophotonic structures have enabled innovative types of flat-optics devices that often outperform the capabilities of bulk components, yet these advances remain ...largely unexplored for quantum applications. We show that nonclassical multiphoton interferences can be achieved at the subwavelength scale in all-dielectric metasurfaces. We simultaneously image multiple projections of quantum states with a single metasurface, enabling a robust reconstruction of amplitude, phase, coherence, and entanglement of multiphoton polarization-encoded states. One- and two-photon states are reconstructed through nonlocal photon correlation measurements with polarization-insensitive click detectors positioned after the metasurface, and the scalability to higher photon numbers is established theoretically. Our work illustrates the feasibility of ultrathin quantum metadevices for the manipulation and measurement of multiphoton quantum states, with applications in free-space quantum imaging and communications.
Huntington's disease (HD) is caused by Huntingtin (Htt) gene mutation resulting in the loss of striatal GABAergic neurons and motor functional deficits. We report here an in vivo cell conversion ...technology to reprogram striatal astrocytes into GABAergic neurons in both R6/2 and YAC128 HD mouse models through AAV-mediated ectopic expression of NeuroD1 and Dlx2 transcription factors. We found that the astrocyte-to-neuron (AtN) conversion rate reached 80% in the striatum and >50% of the converted neurons were DARPP32
medium spiny neurons. The striatal astrocyte-converted neurons showed action potentials and synaptic events, and projected their axons to the targeted globus pallidus and substantia nigra in a time-dependent manner. Behavioral analyses found that NeuroD1 and Dlx2-treated R6/2 mice showed a significant extension of life span and improvement of motor functions. This study demonstrates that in vivo AtN conversion may be a disease-modifying gene therapy to treat HD and other neurodegenerative disorders.
Objective
To determine the impact of the COVID‐19 pandemic on diagnostic and treatment activity in 2020 across hospital providers of prostate cancer (PCa) care in the English National Health Service.
...Methods
Diagnostic and treatment activity between 23 March (start of first national lockdown in England) and 31 December 2020 was compared with the same calendar period in 2019. Patients newly diagnosed with PCa were identified from national rapid cancer registration data linked to other electronic healthcare datasets.
Results
There was a 30.8% reduction (22 419 vs 32 409) in the number of men with newly diagnosed PCa in 2020 after the start of the first lockdown, compared with the corresponding period in 2019. Men diagnosed in 2020 were typically at a more advanced stage (Stage IV: 21.2% vs 17.4%) and slightly older (57.9% vs 55.9% ≥ 70 years; P < 0.001). Prostate biopsies in 2020 were more often performed using transperineal (TP) routes (64.0% vs 38.2%). The number of radical prostatectomies in 2020 was reduced by 26.9% (3896 vs 5331) and the number treated by external beam radiotherapy (EBRT) by 14.1% (9719 vs 11 309). Other changes included an increased use of EBRT with hypofractionation and reduced use of docetaxel chemotherapy in men with hormone‐sensitive metastatic PCa (413 vs 1519) with related increase in the use of enzalutamide.
Conclusion
We found substantial deficits in the number of diagnostic and treatment procedures for men with newly diagnosed PCa after the start of the first lockdown in 2020. The number of men diagnosed with PCa decreased by about one‐third and those diagnosed had more advanced disease. Treatment patterns shifted towards those that limit the risk of COVID‐19 exposure including increased use of TP biopsy, hypofractionated radiation, and enzalutamide. Urgent concerted action is required to address the COVID‐19‐related deficits in PCa services to mitigate their impact on long‐term outcomes.
We demonstrate that a dielectric anapole resonator on a metallic mirror can enhance the third harmonic emission by two orders of magnitude compared to a typical anapole resonator on an insulator ...substrate. By employing a gold mirror under a silicon nanodisk, we introduce a novel characteristic of the anapole mode through the spatial overlap of resonantly excited Cartesian electric and toroidal dipole modes. This is a remarkable improvement on the early demonstrations of the anapole mode in which the electric and toroidal modes interfere off-resonantly. Therefore, our system produces a significant near-field enhancement, facilitating the nonlinear process. Moreover, the mirror surface boosts the nonlinear emission via the free-charge oscillations within the interface, equivalent to producing a mirror image of the nonlinear source and the pump beneath the interface. We found that these improvements result in an extremely high experimentally obtained efficiency of 0.01%.
ObjectivesTo compare gender diversity between UK surgical specialties, assess trends over time, and estimate when gender parity might be achieved.DesignObservational study.SettingNational Health ...Service, UK.ParticipantsNHS Hospital & Community Health Service workforce statistics for 2011 to 2020Main outcome measuresLogistic regression was used to compare female representation in 2020 between surgical specialties, and to examine for any significant trends between 2011 and 2020. The method of least squares was used to estimate when female representation of specialty registrars would reach 50% (‘gender parity’) for specialties with <40% female representation.ResultsIn 2020, female consultant and specialty registrar representation was significantly different between surgical specialties (both p<0.001). Female representation for each specialty were as follows (from highest to lowest): Specialty Registrars—Ophthalmology 49.7%, Otolaryngology 48.2%, Paediatric Surgery 45.5%, Plastic Surgery 42.2%, General Surgery 39.8%, Urology 31.6%, Vascular Surgery 25.0%, Neurosurgery 24.7%, Cardiothoracic Surgery 21.3%, and Trauma and Orthopaedics 20.6%; Consultants—Ophthalmology 32.4%, Paediatric Surgery 31.7%, Plastic Surgery 20.9%, General Surgery 17.5%, Otolaryngology 17%, Vascular Surgery 13.7%, Urology 11.7%, Cardiothoracic Surgery 10.8%, Neurosurgery 8.2%, and Trauma and Orthopaedics 7.3%. There was a significant positive trend in female representation of specialty registrars between 2011 and 2020 for all specialties except for Paediatric Surgery (representation consistently >45%) and Vascular Surgery (representation consistently <30%). General Surgery was estimated to achieve gender parity of their specialty registrars by 2028, Urology by 2033, Neurosurgery by 2064, Trauma and Orthopaedics by 2070, and Cardiothoracic Surgery by 2082.ConclusionsDespite improvements over the last decade, gender disparity persists in the UK surgical workforce and there are significant differences between surgical specialties. Further work is necessary to establish the reasons for these observed differences with a specific focus on Vascular Surgery, Cardiothoracic Surgery, Neurosurgery, and Trauma and Orthopaedics.
Abstract
We reveal that strongly enhanced generation of photon pairs with narrow frequency spectra and sharp angular correlations can be realised through spontaneous parametric down-conversion in ...metasurfaces. This is facilitated by creating meta-gratings through nano-structuring of nonlinear films of sub-wavelength thickness to support the extended bound state in the continuum resonances, associated with ultra-high
Q
-factors, at the biphoton wavelengths across a wide range of emission angles. Such spectral features of photons can be beneficial for various applications, including quantum imaging. Our modelling demonstrates a pronounced enhancement, compared to unpatterned films, of the total photon-pair generation rate normalized to the pump power reaching 1.75 kHz mW
−1
, which is robust with respect to the angular bandwidth of the pump, supporting the feasibility of future experimental realisations.
Patients who "no-show" (NS) clinical appointments are at a high risk of adverse health outcomes. The objective of this study was to evaluate and characterize the relationship between NS visits prior ...to primary total knee arthroplasty (TKA) and 90-day complications after TKA.
We retrospectively reviewed 6,776 consecutive patients undergoing primary TKA. Study groups were separated based on whether patients who NS versus always attended their appointment. A NS was defined as an intended appointment that was not canceled or rescheduled ≤2 hours before the appointment in which the patient did not show. Data collected included total number of follow-up appointments prior to surgery, patient demographics, comorbidities, and 90-day postoperative complications.
Patients who have ≥3 NS appointments had 1.5 times increased odds of a surgical site infection (odds ratio (OR) 1.54, P = .002) compared to always attended patients. Patients who were ≤65 years old (OR: 1.41, P < .001), smokers (OR: 2.01, P < .001), and had a Charlson comorbidity index ≥3 (OR: 4.48, P < .001) were more likely to miss clinical appointments.
Patients who have ≥3 NS appointments prior to TKA had an increased risk for surgical site infection. Sociodemographic factors were associated with higher odds of missing a scheduled clinical appointment. These data suggest that orthopaedic surgeons should consider NS data as an important clinical decision-making tool to assess risk for postoperative complications to minimize complications following TKA.
The extent of variation in DNA methylation patterns in healthy individuals is not yet well documented. Identification of inter-individual epigenetic variation is important for understanding ...phenotypic variation and disease susceptibility. Using neutrophils from a cohort of healthy individuals, we generated base-resolution DNA methylation maps to document inter-individual epigenetic variation. We identified 12851 autosomal inter-individual variably methylated fragments (iVMFs). Gene promoters were the least variable, whereas gene body and upstream regions showed higher variation in DNA methylation. The iVMFs were relatively enriched in repetitive elements compared to non-iVMFs, and were associated with genome regulation and chromatin function elements. Further, variably methylated genes were disproportionately associated with regulation of transcription, responsive function and signal transduction pathways. Transcriptome analysis indicates that iVMF methylation at differentially expressed exons has a positive correlation and local effect on the inclusion of that exon in the mRNA transcript.
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