Approach to Treatment of Cervical Pregnancy: A Case Report

CASE: A 25yo G1 at 11wk4d dated by LMP and confirmed with a 10 week ultrasound presents with a possible cervical ectopic pregnancy. Past medical, surgical, and OBGYN histories are unremarkable. A cervical pregnancy was suspected on ultrasound due to low implantation of the gestational sac, and a significant posterior bulge with an hourglass shaped uterus. MRI suggested implantation of the placenta in the posterior uterine and cervical wall due to extreme thinning of these structures. Our institution had previously created a protocol for multidisciplinary management of cesarean scar and cervical pregnancies. She desires fertility preservation, and so consented to combined local and systemic treatment with Methotrexate (MTX). Preprocedural Beta-hCG was 81,514.8 mU/mL. Ultrasound-guided transvaginal intra-gestational sac injection of MTX was performed without complication, though cardiac activity was still present at the conclusion of the procedure. The patient also received an IM injection of MTX before discharge. Serial Beta-hCG are still being followed, and are trending towards zero. CONCLUSION: The optimal management for cervical pregnancies is not known, and decisions around type of management are informed by the patient’s desire for fertility preservation. In this case, a protocol created by a multidisciplinary team was used to guide treatment. This protocol using MTX successfully treated the cervical pregnancy at 11wk4d and avoided a surgery that could complicate future fertility. CLINICAL SIGNIFICANCE: Due to the rare occurrence of cervical pregnancy, there is not a universally accepted treatment protocol. This case shows that medical management can be successful for cervical pregnancies. Clear guidelines must be established for cervical pregnancies to optimize outcomes, and decrease maternal morbidity and mortality and to preserve future fertility

Impact of the government's restrictions and guidance in relation to “social distancing” on the lives of ethnic minority populations:A mixed methods study

Background and Aims: The impacts of the COVID-19 pandemic have not been equal, with a disproportionate impact among ethnic minority communities. Structural inequalities in social determinants of health such as housing and employment have contributed to COVID-19's impact on deprived communities, including many ethnic minority communities. To compare (1) how the UK government's “social distancing” restrictions and guidance were perceived and implemented by ethnic minority populations compared to white populations, (2) the impact of restrictions and guidance upon these groups. Methods: An explanatory sequential mixed methods study incorporated a quantitative survey and qualitative semi-structured interviews to explore individual perceptions and experiences of COVID-19 and the national restrictions. Survey participants (n = 1587) were recruited from North West England; 60 (4%) participants were from ethnic minority communities. Forty-nine interviews were conducted; 19 (39%) participants were from ethnic minority communities. Interviews were transcribed verbatim and analysed using a thematic approach. Data collection was between April and August 2020. Results: Significant differences in demographics and household overcrowding were observed between white vs ethnic minority survey respondents, who were also significantly less confident in their knowledge of COVID-19, less likely to be high-risk drinkers, and marginally more likely to have experienced job loss and/or reduced household income. There were no group differences in wellbeing, perceptions, or nonfinancial impacts. Two inter-related themes included: (1) government guidance, incorporating people's knowledge and understanding of the guidance and their confusion/frustration over messaging; (2) the impacts of restrictions on keyworkers, home-schooling, working from home and changes in lifestyle/wellbeing. Conclusions: Further research is needed on the long-term impacts of COVID-19 on ethnic minority communities. If policy responses to COVID-19 are to benefit ethnic minority communities, there is a need for future studies to consider fundamental societal issues, such as the role of housing and economic disadvantage.</p

Post-mortem correlates of in vivo PiB-PET amyloid imaging in a typical case of Alzheimer's disease

The positron emission tomography (PET) radiotracer Pittsburgh Compound-B (PiB) binds with high affinity to β-pleated sheet aggregates of the amyloid-β (Aβ) peptide in vitro. The in vivo retention of PiB in brains of people with Alzheimer's disease shows a regional distribution that is very similar to distribution of Aβ deposits observed post-mortem. However, the basis for regional variations in PiB binding in vivo, and the extent to which it binds to different types of Aβ-containing plaques and tau-containing neurofibrillary tangles (NFT), has not been thoroughly investigated. The present study examined 28 clinically diagnosed and autopsy-confirmed Alzheimer's disease subjects, including one Alzheimer's disease subject who had undergone PiB-PET imaging 10 months prior to death, to evaluate region- and substrate-specific binding of the highly fluorescent PiB derivative 6-CN-PiB. These data were then correlated with region-matched Aβ plaque load and peptide levels, [3H]PiB binding in vitro, and in vivo PET retention levels. We found that in Alzheimer's disease brain tissue sections, the preponderance of 6-CN-PiB binding is in plaques immunoreactive to either Aβ42 or Aβ40, and to vascular Aβ deposits. 6-CN-PiB labelling was most robust in compact/cored plaques in the prefrontal and temporal cortices. While diffuse plaques, including those in caudate nucleus and presubiculum, were less prominently labelled, amorphous Aβ plaques in the cerebellum were not detectable with 6-CN-PiB. Only a small subset of NFT were 6-CN-PiB positive; these resembled extracellular ‘ghost’ NFT. In Alzheimer's disease brain tissue homogenates, there was a direct correlation between [3H]PiB binding and insoluble Aβ peptide levels. In the Alzheimer's disease subject who underwent PiB-PET prior to death, in vivo PiB retention levels correlated directly with region-matched post-mortem measures of [3H]PiB binding, insoluble Aβ peptide levels, 6-CN-PiB- and Aβ plaque load, but not with measures of NFT. These results demonstrate, in a typical Alzheimer's disease brain, that PiB binding is highly selective for insoluble (fibrillar) Aβ deposits, and not for neurofibrillary pathology. The strong direct correlation of in vivo PiB retention with region-matched quantitative analyses of Aβ plaques in the same subject supports the validity of PiB-PET imaging as a method for in vivo evaluation of Aβ plaque burden

Spatially Explicit Analyses of Anopheline Mosquitoes Indoor Resting Density: Implications for Malaria Control

Background: The question of sampling and spatial aggregation of malaria vectors is central to vector control efforts and estimates of transmission. Spatial patterns of anopheline populations are complex because mosquitoes' habitats and behaviors are strongly heterogeneous. Analyses of spatially referenced counts provide a powerful approach to delineate complex distribution patterns, and contributions of these methods in the study and control of malaria vectors must be carefully evaluated. Methodology/Principal Findings: We used correlograms, directional variograms, Local Indicators of Spatial Association (LISA) and the Spatial Analysis by Distance IndicEs (SADIE) to examine spatial patterns of Indoor Resting Densities (IRD) in two dominant malaria vectors sampled with a 565 km grid over a 2500 km(2) area in the forest domain of Cameroon. SADIE analyses revealed that the distribution of Anopheles gambiae was different from regular or random, whereas there was no evidence of spatial pattern in Anopheles funestus (Ia = 1.644, Pa0.05, respectively). Correlograms and variograms showed significant spatial autocorrelations at small distance lags, and indicated the presence of large clusters of similar values of abundance in An. gambiae while An. funestus was characterized by smaller clusters. The examination of spatial patterns at a finer spatial scale with SADIE and LISA identified several patches of higher than average IRD (hot spots) and clusters of lower than average IRD (cold spots) for the two species. Significant changes occurred in the overall spatial pattern, spatial trends and clusters when IRDs were aggregated at the house level rather than the locality level. All spatial analyses unveiled scale-dependent patterns that could not be identified by traditional aggregation indices. Conclusions/Significance: Our study illustrates the importance of spatial analyses in unraveling the complex spatial patterns of malaria vectors, and highlights the potential contributions of these methods in malaria control

Associations with drug use and sexualised drug use among women who have sex with women (WSW) in the UK: Findings from the LGBT Sex and Lifestyles Survey

Introduction Studies indicate that women who have sex with women (WSW) report greater levels of drug use than heterosexual women, but globally few studies have looked at sexualised drug use among WSW. This study investigated the factors associated with drug use and sexualised drug use (SDU) among WSW. Methods Potential participants across the UK were invited to take part in a cross-sectional anonymous online survey between April-June 2018. The LGBT Sex and Lifestyles Survey recruited participants through Facebook advertising and social media posts from community organisations. Multivariate logistic regression was used to compare WSW who had engaged in any drug use in the past 12 months with those who had not, and those who engaged in sexualised drug use in the past 12 months with those who engaged in other drug use. Results: 1501 WSW could be included in the analyses (mean age = 28.9, 97% white ethnicity). Any drug use was reported by 39% of WSW (n = 583), 44% of which (17% of total, n = 258) reported SDU. Factors associated with drug use were identifying as queer (aOR = 1.86, 95%CI 1.08, 3.23), younger age (aOR = 0.96, 95%CI 0.95, 0.98), being born outside the UK (aOR = 1.75, 95%CI 1.15, 2.66), recent sexual assault (aOR = 2.35, 95%CI 1.43, 3.86), > = 5 female sexual partners (aOR = 3.81, 95%CI 1.81, 8.01), and psychological distress (aOR = 1.75, 95%CI 1.15, 2.67). SDU was associated with identifying as bisexual (aOR = 2.55, 95%CI 1.69, 3.86), > = 5 female sexual partners (aOR = 4.50, 95%CI 1.91, 10.59), and highest education achieved at 16 or lower (aOR = 2.46, 95%CI 1.24, 4.90). Conclusions: Some WSW may have negative experiences in relation to drug use and SDU. Harm reduction and health services that provide services for WSW should be aware of potentially compounding factors related to drug use, such as sexual assault and psychological distress, providing a safe and LGBT-friendly environment to discuss these issues

Speech Communication

Contains table of contents for Part IV, table of contents for Section 1 and reports on five research projects.Apple Computer, Inc.C.J. Lebel FellowshipNational Institutes of Health (Grant T32-NS07040)National Institutes of Health (Grant R01-NS04332)National Institutes of Health (Grant R01-NS21183)National Institutes of Health (Grant P01-NS23734)U.S. Navy / Naval Electronic Systems Command (Contract N00039-85-C-0254)U.S. Navy - Office of Naval Research (Contract N00014-82-K-0727

Developing Global Maps of the Dominant Anopheles Vectors of Human Malaria

Simon Hay and colleagues describe how the Malaria Atlas Project has collated anopheline occurrence data to map the geographic distributions of the dominant mosquito vectors of human malaria

Training future generations to deliver evidence-based conservation and ecosystem management

1. To be effective, the next generation of conservation practitioners and managers need to be critical thinkers with a deep understanding of how to make evidence-based decisions and of the value of evidence synthesis. 2. If, as educators, we do not make these priorities a core part of what we teach, we are failing to prepare our students to make an effective contribution to conservation practice. 3. To help overcome this problem we have created open access online teaching materials in multiple languages that are stored in Applied Ecology Resources. So far, 117 educators from 23 countries have acknowledged the importance of this and are already teaching or about to teach skills in appraising or using evidence in conservation decision-making. This includes 145 undergraduate, postgraduate or professional development courses. 4. We call for wider teaching of the tools and skills that facilitate evidence-based conservation and also suggest that providing online teaching materials in multiple languages could be beneficial for improving global understanding of other subject areas.Peer reviewe

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice