Dynamics of genotype-specific HPV clearance and reinfection in rural Ghana may compromise HPV screening approaches

Persistent Human Papillomavirus (HPV) infection is a prerequisite for cervical cancer development. Few studies investigated clearance of high-risk HPV in low-and-middle-income countries. Our study investigated HPV clearance and persistence over four years in women from North Tongu District, Ghana. In 2010/2011, cervical swabs of 500 patients were collected and HPV genotyped (nested multiplex PCR) in Accra, Ghana. In 2014, 104 women who previously tested positive for high-risk HPV and remained untreated were re-tested for HPV. Cytobrush samples were genotyped (GP5+/6+ PCR & Luminex-MPG readout) in Berlin, Germany. Positively tested patients underwent colposcopy and treatment if indicated. Of 104 women, who tested high-risk HPV+ in 2010/2011, seven (6,7%; 95%CI: 2.7-13.4%) had ≥1 persistent high-risk-infection after ~4 years (mean age 39 years). Ninety-seven (93,3%; 95%CI: 86.6-97.3%) had cleared the original infection, while 22 (21.2%; 95%CI: 13.8-30.3%) had acquired new high-risk infections with other genotypes. Persistent types found were HPV 16, 18, 35, 39, 51, 52, 58, and 68. Among those patients, one case of CIN2 (HPV 68) and one micro-invasive cervical cancer (HPV 16) were detected. This longitudinal observational data suggest that single HPV screening rounds may lead to over-referral. Including type-specific HPV re-testing or additional triage methods could help reduce follow-up rates

The Risk Assessment and Prediction Tool (RAPT) for Discharge Planning in a Posterior Lumbar Fusion Population

BACKGROUND: As the use of bundled care payment models has become widespread in neurosurgery, there is a distinct need for improved preoperative predictive tools to identify patients who will not benefit from prolonged hospitalization, thus facilitating earlier discharge to rehabilitation or nursing facilities.OBJECTIVE: To validate the use of Risk Assessment and Prediction Tool (RAPT) in patients undergoing posterior lumbar fusion for predicting discharge disposition.METHODS: Patients undergoing elective posterior lumbar fusion from June 2016 to February 2017 were prospectively enrolled. RAPT scores and discharge outcomes were recorded for patients aged 50 yr or more (n = 432). Logistic regression analysis was used to assess the ability of RAPT score to predict discharge disposition. Multivariate regression was performed in a backwards stepwise logistic fashion to create a binomial model.RESULTS: Escalating RAPT score predicts disposition to home (P \u3c .0001). Every unit increase in RAPT score increases the chance of home disposition by 55.8% and 38.6% than rehab and skilled nursing facility, respectively. Further, RAPT score was significant in predicting length of stay (P = .0239), total surgical cost (P = .0007), and 30-d readmission (P \u3c .0001). Amongst RAPT score subcomponents, walk, gait, and postoperative care availability were all predictive of disposition location (P \u3c .0001) for both models. In a generalized multiple logistic regression model, the 3 top predictive factors for disposition were the RAPT score, length of stay, and age (P \u3c .0001, P \u3c .0001 and P = .0001, respectively).CONCLUSION: Preoperative RAPT score is a highly predictive tool in lumbar fusion patients for discharge disposition

Discovery and Follow-up Observations of the Young Type Ia Supernova 2016coj

The Type~Ia supernova (SN~Ia) 2016coj in NGC 4125 (redshift $z=0.004523$) was discovered by the Lick Observatory Supernova Search 4.9 days after the fitted first-light time (FFLT; 11.1 days before $B$-band maximum). Our first detection (pre-discovery) is merely $0.6\pm0.5$ day after the FFLT, making SN 2016coj one of the earliest known detections of a SN Ia. A spectrum was taken only 3.7 hr after discovery (5.0 days after the FFLT) and classified as a normal SN Ia. We performed high-quality photometry, low- and high-resolution spectroscopy, and spectropolarimetry, finding that SN 2016coj is a spectroscopically normal SN Ia, but with a high velocity of \ion{Si}{2} $\lambda$6355 ($\sim 12,600$\,\kms\ around peak brightness). The \ion{Si}{2} $\lambda$6355 velocity evolution can be well fit by a broken-power-law function for up to a month after the FFLT. SN 2016coj has a normal peak luminosity ($M_B \approx -18.9 \pm 0.2$ mag), and it reaches a $B$-band maximum \about16.0~d after the FFLT. We estimate there to be low host-galaxy extinction based on the absence of Na~I~D absorption lines in our low- and high-resolution spectra. The spectropolarimetric data exhibit weak polarization in the continuum, but the \ion{Si}{2} line polarization is quite strong ($\sim 0.9\% \pm 0.1\%$) at peak brightness.Comment: Submitte

Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits

Background Height and other anthropometric measures are consistently found to associate with differential cancer risk. However, both genetic and mechanistic insights into these epidemiological associations are notably lacking. Conversely, inherited genetic variants in tumour suppressors and oncogenes increase cancer risk, but little is known about their influence on anthropometric traits. Methods By integrating inherited and somatic cancer genetic data from the Genome-Wide Association Study Catalog, expression Quantitative Trait Loci databases and the Cancer Gene Census, we identify SNPs that associate with different cancer types and differential gene expression in at least one tissue type, and explore the potential pleiotropic associations of these SNPs with anthropometric traits through SNP-wise association in a cohort of 500,000 individuals. Results We identify three regulatory SNPs for three important cancer genes, FANCA, MAP3K1 and TP53 that associate with both anthropometric traits and cancer risk. Of particular interest, we identify a previously unrecognised strong association between the rs78378222[C] SNP in the 3' untranslated region (3'-UTR) of TP53 and both increased risk for developing non-melanomatous skin cancer (OR=1.36 (95% 1.31 to 1.41), adjusted p=7.62E−63), brain malignancy (OR=3.12 (2.22 to 4.37), adjusted p=1.43E−12) and increased standing height (adjusted p=2.18E−24, beta=0.073±0.007), lean body mass (adjusted p=8.34E−37, beta=0.073±0.005) and basal metabolic rate (adjusted p=1.13E−31, beta=0.076±0.006), thus offering a novel genetic link between these anthropometric traits and cancer risk. Conclusion Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a genetic basis for linking these human phenotypes

A Cluster Randomized Trial of Routine HIV-1 Viral Load Monitoring in Zambia: Study Design, Implementation, and Baseline Cohort Characteristics

The benefit of routine HIV-1 viral load (VL) monitoring of patients on antiretroviral therapy (ART) in resource-constrained settings is uncertain because of the high costs associated with the test and the limited treatment options. We designed a cluster randomized controlled trial to compare the use of routine VL testing at ART-initiation and at 3, 6, 12, and 18 months, versus our local standard of care (which uses immunological and clinical criteria to diagnose treatment failure, with discretionary VL testing when the two do not agree).Dedicated study personnel were integrated into public-sector ART clinics. We collected participant information in a dedicated research database. Twelve ART clinics in Lusaka, Zambia constituted the units of randomization. Study clinics were stratified into pairs according to matching criteria (historical mortality rate, size, and duration of operation) to limit the effect of clustering, and independently randomized to the intervention and control arms. The study was powered to detect a 36% reduction in mortality at 18 months.From December 2006 to May 2008, we completed enrollment of 1973 participants. Measured baseline characteristics did not differ significantly between the study arms. Enrollment was staggered by clinic pair and truncated at two matched sites.A large clinical trial of routing VL monitoring was successfully implemented in a dynamic and rapidly growing national ART program. Close collaboration with local health authorities and adequate reserve staff were critical to success. Randomized controlled trials such as this will likely prove valuable in determining long-term outcomes in resource-constrained settings.Clinicaltrials.gov NCT00929604

Pandemic fatigue impedes mitigation of COVID-19 in Hong Kong

Hong Kong has implemented stringent public health and social measures (PHSMs) to curb each of the four COVID-19 epidemic waves since January 2020. The third wave between July and September 2020 was brought under control within 2 m, while the fourth wave starting from the end of October 2020 has taken longer to bring under control and lasted at least 5 mo. Here, we report the pandemic fatigue as one of the potential reasons for the reduced impact of PHSMs on transmission in the fourth wave. We contacted either 500 or 1,000 local residents through weekly random-digit dialing of landlines and mobile telephones from May 2020 to February 2021. We analyze the epidemiological impact of pandemic fatigue by using the large and detailed cross-sectional telephone surveys to quantify risk perception and self-reported protective behaviors and mathematical models to incorporate population protective behaviors. Our retrospective prediction suggests that an increase of 100 daily new reported cases would lead to 6.60% (95% CI: 4.03, 9.17) more people worrying about being infected, increase 3.77% (95% CI: 2.46, 5.09) more people to avoid social gatherings, and reduce the weekly mean reproduction number by 0.32 (95% CI: 0.20, 0.44). Accordingly, the fourth wave would have been 14% (95% CI%: −53%, 81%) smaller if not for pandemic fatigue. This indicates the important role of mitigating pandemic fatigue in maintaining population protective behaviors for controlling COVID-19

CAMEMBERT: A Mini-Neptunes GCM Intercomparison, Protocol Version 1.0. A CUISINES Model Intercomparison Project

With an increased focus on the observing and modelling of mini-Neptunes, there comes a need to better understand the tools we use to model their atmospheres. In this paper, we present the protocol for the CAMEMBERT (Comparing Atmospheric Models of Extrasolar Mini-neptunes Building and Envisioning Retrievals and Transits) project, an intercomparison of general circulation models (GCMs) used by the exoplanetary science community to simulate the atmospheres of mini-Neptunes. We focus on two targets well studied both observationally and theoretically with planned JWST Cycle 1 observations: the warm GJ~1214b and the cooler K2-18b. For each target, we consider a temperature-forced case, a clear sky dual-grey radiative transfer case, and a clear sky multi band radiative transfer case, covering a range of complexities and configurations where we know differences exist between GCMs in the literature. This paper presents all the details necessary to participate in the intercomparison, with the intention of presenting the results in future papers. Currently, there are eight GCMs participating (ExoCAM, Exo-FMS, FMS PCM, Generic PCM, MITgcm, RM-GCM, THOR, and the UM), and membership in the project remains open. Those interested in participating are invited to contact the authors.Comment: Accepted to PS

Mediator Condensates Localize Signaling Factors to Key Cell Identity Genes

The gene expression programs that define the identity of each cell are controlled by master transcription factors (TFs) that bind cell-type-specific enhancers, as well as signaling factors, which bring extracellular stimuli to these enhancers. Recent studies have revealed that master TFs form phase-separated condensates with the Mediator coactivator at super-enhancers. Here, we present evidence that signaling factors for the WNT, TGF-β, and JAK/STAT pathways use their intrinsically disordered regions (IDRs) to enter and concentrate in Mediator condensates at super-enhancers. We show that the WNT coactivator β-catenin interacts both with components of condensates and DNA-binding factors to selectively occupy super-enhancer-associated genes. We propose that the cell-type specificity of the response to signaling is mediated in part by the IDRs of the signaling factors, which cause these factors to partition into condensates established by the master TFs and Mediator at genes with prominent roles in cell identity