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Purpose Information on incentives for COVID-19 testing is needed to understand effective practices that encourage testing uptake. We describe characteristics of those who received an incentive after performing a rapid antigen test. Design Cross-sectional descriptive analysis of survey data. Setting During April 29–May 9, 2021, COVID-19 rapid antigen testing was offered in 2 Maryland cities. Sample Convenience sample of 553 adults (≥18 years) who tested and received an incentive; 93% consented to survey. Measures Survey questions assessed reasons for testing, testing history, barriers, and demographics. Analysis Robust Poisson regressions were used to determine characteristic differences based on testing history and between participants who would re-test in the future without an incentive vs participants who would not. Results The most common reasons for testing were the desire to be tested (n = 280; 54%) and convenience of location (n = 146; 28%). Those motivated by an incentive to test (n = 110; 21%) were 5.83 times as likely to state they would not test again without an incentive, compared to those with other reasons for testing (95% CI: 2.67-12.72, P < .001). Critical Limitations No comparative study group. Conclusion Results indicate internal motivation and convenience were prominent factors supporting testing uptake. Incentives may increase community testing participation, particularly among people who have never tested. Keywords COVID-19, pandemic, incentives, health behavior, community testing.

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic-resistant bacterial infections acquired during hospital stays have increased. Antibiotic adjuvants are a key strategy to combat these bacteria. We have evaluated several small molecule antibiotic adjuvants that have strong potentiation with β-lactam antibiotics and are likely inhibiting a master regulatory kinase, Stk1. Here, we investigated how the lead adjuvant (compound 8) exerts its effects in a more comprehensive manner. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with oxacillin and the adjuvant. Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up- and downregulated, respectively, in response to cotreatment. Gene ontology categories and biochemical pathways that were significantly enriched with downregulated genes involved carbohydrate utilization, such as the citrate cycle and the phosphotransferase system. One of the most populated pathways was S. aureus infection. Results from an interaction network constructed with affected gene products supported the hypothesis that Stk1 is a target of compound 8. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect due to Stk1 inhibition. These results point to this antibiotic adjuvant having potential broad therapeutic use in combatting MRSA.

Antibiotic-resistant infections are a pressing global concern, causing millions of deaths each year. Methicillin-resistant

The global coronavirus SARS-CoV2 (COVID-19) pandemic outbreak caused immediate, far-reaching social schisms and created unprecedented challenges for hospital social work services worldwide. Existing hospital disaster plans were inadequately equipped for pandemics and organisational plans needed to quickly adapt to respond to the increased clinical demands and unique logistical considerations triggered by the virus. Literature reviews provided little in the way of precise guidance for practitioners. Hospital social workers responded not only to a new cohort of patients, but also to all patients affected by the societal repercussions of the pandemic and by governments’ attempts to mitigate the impacts of the virus. Psychosocial assessments, the bedrock of social work intervention, needed to adapt and evolve to encompass and address the exacerbation of existing social risks in new ways. This article originated from the authors’ interest in identifying practice implications for hospital social work during the COVID-19 pandemic. The authors briefly outline the distinct impact of COVID-19 on psychosocial issues such as domestic and family violence, elder abuse, child protection, financial stress and social isolation. They create a forum of international hospital social work centres to develop a consensus approach for addressing these issues in the context of a social work psychosocial assessment.

Introduction: Primitive asteroids that accreted beyond the snowline in the protoplanetary disk likely played a crucial role in the delivery of water and organic matter to Earth and other terrestrial planets. The surface of the Cb-type asteroid 162173 Ryugu has low overall reflectance and an absorption feature at ~2.7 µm consistent with the presence of carbonaceous materials and phyllosilicates [1]. The spectral characteristics of Ryugu’s surface are most similar to the highly altered CI (“Ivuna-like”) and/or dehydrated CY (“Yamato-like”) carbonaceous chondrites [2]. In December 2020, JAXA’s Hayabusa2 mission successfully returned to Earth with >5 g of sample collected from the surface of Ryugu. The initial investigation of the samples suggested a close affinity with the CI chondrites [3], which consist of abundant phyllosilicates (~80 vol.%), plus minor amounts of magnetite (~10 vol.%), and dolomite (500°C [5]. Here, as part of the Hayabusa2 “Stone” preliminary examination team, we have characterised the modal mineralogy of a Ryugu particle to further constrain its aqueous and thermal history. Methods: A powdered sub-sample of Ryugu particle C0002 (plates 3 and 4) was analysed using position-sensitive-detector X-ray diffraction (PSD-XRD) at the Natural History Museum (NHM), London. XRD patterns were acquired from the Ryugu powder using a high-intensity micro X-ray source for 6 hours, with the sample rotated throughout the analysis. Pure standards of each phase detected in the Ryugu powder were analysed under exactly the same conditions for 15 minutes. The modal mineralogy of the Ryugu powder was then determined using an established peak fitting method [4, 5]. Results & Discussion: Ryugu particle C0002 (plates 3 and 4) contains a mixture of Mg-rich serpentines and smectites that are present at an abundance of ~84 (± 2) vol.%. Other phases identified from the XRD pattern include magnetite (~8 vol.%), pyrrhotite (~7 vol.%), and dolomite (~2 vol.%). This mineralogy is broadly consistent with our petrographic observations of polished Ryugu sections (C0025-01 and C0103-02). Diffraction peaks from anhydrous olivine and pyroxene were not observed suggesting that their abundance is ≤1 vol.% in the analysed fraction of C0002. If we assume a maximum anhydrous silicate abundance of 2 vol.%, then the phyllosilicate fraction (PSF = total phyllosilicate abundance / [total anhydrous silicate + total phyllosilicate abundance]) of the Ryugu powder is 0.98, which corresponds to a petrologic sub-type of 1.1 on the alteration scale of Howard et al. [6]. The XRD pattern and modal mineralogy of Ryugu particle C0002 (plates 3 and 4) is very similar to the CI chondrites [4]. However, the Ryugu powder does not contain sulphates and ferrihydrite, which are common in the CI chondrites and thought to be terrestrial weathering products [7]. The Ryugu powder also has a comparable mineralogy to the recent C2ung fall Tarda, which appears to be related to the Tagish Lake (C2ung) meteorite [8]. However, Tarda retains partially altered chondrules and has a relatively high abundance of anhydrous silicates (~10 vol.%) [9]. In addition, the XRD pattern and modal mineralogy of the Ryugu powder is clearly distinct from the CY chondrites, which contain dehydrated phyllosilicates that lack coherent diffraction, and abundant poorly crystalline troilite and secondary olivine [5]. The modal mineralogy of Ryugu particle C0002 (plates 3 and 4) is consistent with having formed through low temperature aqueous alteration. The fluid-rock reactions reached near-completion, resulting in a secondary assemblage of phyllosilicate, sulphide, magnetite, and Mg-carbonate that was not overprinted by a later episode of thermal metamorphism at temperatures >~400°C. References: [1] Kitazato et al. (2019) Science. 364:272. [2] Kitazato et al. (2021) Nature Astronomy. 5:246. [3] Yada et al. (2022) Nature Astronomy. 6:214. [4] King et al. (2015) Geochimica et Cosmochimica Acta. 165:148. [5] King et al. (2019) Geochemistry. 79:125531. [6] Howard et al. (2015) Geochimica et Cosmochimica Acta. 149:206. [7] Gounelle & Zolensky (2001) Meteoritics & Planetary Science. 36:1321. [8] Marrocchi et al. (2021) The Astrophysical Journal Letters 913:L9. [9] King et al. (2021) 52nd LPSC, abstract #1909.

A new Roadmap for Solar System Research in the UK has been published, and the Solar System Advisory Panel report on the processes involved in updating the previous iteration

Methicillin-resistant Staphylococcus aureus (MRSA) is a major threat to human health, as the US mortality rate outweighs those from HIV, tuberculosis, and viral hepatitis combined. In the wake of the COVID-19 pandemic, antibiotic resistant bacterial infections acquired during hospital stays have increased. Instead of designing and deploying new antibiotics which MRSA would quickly develop resistance to, adjuvants are a key strategy to combatting these bacteria. We have evaluated several small molecule antibiotic adjuvants that have strong potentiation with β-lactam antibiotics and are likely inhibiting a master regulatory kinase, Stk1. Here, we investigated how the lead adjuvant exerts its effects in a more comprehensive manner. We hypothesized that the expression levels of key resistance genes would decrease once cotreated with a β-lactam antibiotic (oxacillin) and the adjuvant (compound 8). Furthermore, bioinformatic analyses would reveal biochemical pathways enriched in differentially expressed genes. RNA-seq analysis showed 176 and 233 genes significantly up and downregulated, respectively, in response to cotreatment with compound 8 and oxacillin compared to oxacillin alone. Gene ontology categories that were significantly enriched among downregulated genes involved phosphotransferase systems. Most of the biochemical pathways enriched with significantly downregulated genes involved carbohydrate utilization, such as the citrate cycle and the phosphotransferase system. One of the most populated pathways was S. aureus infection. Results from an interaction network constructed with affected gene products supported the hypothesis that Stk1 is a target of compound 8. This study revealed a dramatic impact of our lead adjuvant on the transcriptome that is consistent with a pleiotropic effect due to Stk1 inhibition. These results point to this antibiotic adjuvant having potential broad therapeutic use in combatting MRSA.

International audience; On April 23rd, 2019, the Aguas Zarcas meteorite fall occurred in Costa Rica. Because the meteorite was quickly recovered, it contains valuable extraterrestrial materials that have not been contaminated by terrestrial processes. Our X-ray computed tomography (XCT) and scanning electron microscopy (SEM) results on various pre-rain fragments from earlier work (Kerraouch et al., 2020; 2021) revealed several distinct lithologies: Two distinct metal-rich lithologies (Met-1 and Met-2), a CM1/2 lithology, a C1 lithology, and a brecciated CM2 lithology consisting of different petrologic types. Here, we further examined these lithologies in the brecciated Aguas Zarcas meteorite and report new detailed mineralogical, chemical, isotopic, and organic matter characteristics. In addition to petrographic differences, the lithologies also display different chemical and isotopic compositions. The variations in their bulk oxygen isotopic compositions indicate that the various lithologies formed in different environments and/or under diverse conditions (e.g., water/rock ratios). Each lithology experienced a different hydration period during its evolution. Together, this suggests that multiple precursor parent bodies may have been involved in these processes of impact brecciation, mixing, and re-assembly. The Cr and Ti isotopic data for both the CM1/2 and Met-1 lithology are consistent with those of other CM chondrites, even though Met-1 displays a significantly lower ε50Ti isotopic composition that may be attributable to sample heterogeneities on the bulk meteorite scale and may reflect variable abundances of refractory phases in the different lithologies of Aguas Zarcas. Finally, examination of the organic matter of the various lithologies also suggests no strong evidence of thermal events, but a short-term heating cannot completely be excluded. Raman parameters indicate that the peak temperature has been lower than that for Yamato-793321 (CM2, ∼400 °C). Considering the new information presented in this study, we now better understand the origin and formation history of the Aguas Zarcas daughter body.

To measure the association between intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to long-term care facility (LTCF) residents recently diagnosed with pre-symptomatic, mild-to-moderate COVID-19 and are considered high risk for disease progression with mortality, hospitalization, and adverse effects. A retrospective analysis of LTCF residents with confirmed COVID-19, pre-symptomatic, mild to moderate disease, who were treated with bamlanivimab (LY-CoV555) were compared to similar LTCF residents who did not receive monoclonal antibody treatment. Dependent variables investigated included mortality and hospitalization as primary outcomes with adverse effects as the secondary outcome. A total of 107 residents from three LTCFs were diagnosed with pre-symptomatic, mild-to-moderate COVID-19 between November 1, 2020, and December 31, 2020. Of the 107 study participants, 44 residents provided consent to treatment, of which 39 received a single intravenous infusion of neutralizing monoclonal antibody, bamlanivimab 700mg, early in the disease, and 5 received an incomplete dose. Of the 39 residents who received the full dose of bamlanivimab, 5 (12.8%) were admitted to the hospital and 4 (10.3%) died. Conversely, of the 63 residents who did not receive the monoclonal antibody, 26 (41.3 %) were admitted to the hospital and 18 (28.6%) died. Relative risk for hospitalization and death were statistically significantly lower for those residents who received the full bamlanivimab treatment. No serious adverse effects were documented on any patient. Intravenous administration of monoclonal antibody bamlanivimab (LY-CoV555) to LTCF residents recently diagnosed with pre-symptomatic, mild to moderate COVID-19 was significantly associated with reduced mortality and hospitalization. The monoclonal antibody was well-tolerated.

Main text The UK has a long history of meteorite falls (where the meteorite fireball is witnessed, and the stone recovered, dating back to 1623 (MetBull, 2020). But the last meteorite fall in the UK was nearly 30 years ago when the Glatton stone, an L6 ordinary chondrite was recovered in 1991 (Hutchinson et al., 1991). Meteorite falls are important samples as they are usually recovered within days of the fireball event. As such, they have not experienced the deleterious effects terrestrial weathering that can change their extraterrestrial mineralogy, chemistry and isotopic composition (Bland et al., 2006). In exceptional circumstances rapidly recovered falls may have avoided rainfall so that soluble extraterrestrial minerals such as salts may be preserved (Chan et al., 2018). Therefore, meteorite falls represent much more pristine extraterrestrial material than their find counterparts within the same group, and consequently, characterisation of their texture and chemical signatures provides a clearer window into solar system processes. However, even falls are limited in their interpretive power as the geological context of the stone (i.e. where in the solar system it originated from) is unknown. To derive this contextual information requires the imaging of the fireball event from multiple geographical positions (Devillepoix et al., 2020). This data provides two vital pieces of information; the initial orbit of the meteoroid can be calculated and the final fall position can be predicted with increased accuracy (Devillepoix et al., 2020). As such, dedicated fireball camera networks (Bowden, 2006) are entering ‘a golden age’ with improvements in hardware and software capabilities as well as a reduction in production costs (Spurný et al., 2014). Continent-scale observatories have been established (Howie et al., 2017) and global networks are under construction (Devillepoix et al., 2020). In addition, these same developments have enabled the amateur astronomy community to construct their own networks either as groups or individuals with functional data pipelines and observations that can rival funded networks. Consequently, the number of recovered meteorite falls with orbits globally has grown rapidly over recent years (Borovička et al., 2015). The UK is a hotbed for such activity but does not have a recent recovered meteorite fall…yet. There are currently two active academically funded networks in the UK: the UK Fireball Network (UKFN: part of the Global Fireball Observatory built on the hardware and software developed by the Desert Fireball Network in Australia), and the System for Capture of Asteroid and Meteorite Paths (SCAMP; the UK arm of the French-led Fireball Recovery and InterPlanetary Observation Network (FRIPON)) (Figure 1, 2). In addition, there are two major amateur networks the UK Meteor Observation Network (UKMON), and NEMETODE, as well as an emerging presence of the Raspberry-Pi based Global Meteor Network and countless individual citizen scientists also imaging the UK night skies (Figure 1, 2). However, environmental factors in the UK such as light pollution and regular low-lying cloud cover means that a single fireball may not be captured multiple times by one network, preventing them from calculating an orbit and accurate fall position. As such, these networks, together with UK planetary scientists and National museums, have formed a collaborative data-sharing initiative called the UK Fireball Alliance (UKFAll) in order to maximise the chances of capturing a meteorite-dropping fireball event that makes landfall on the UK. Since the initiation of UKFAll in late 2018 many joint fireball observations have been made between UK networks including a fireball on the 16th February 2020 that likely dropped a few 10s of grams of extraterrestrial material into the North Sea (Figure 3). However, the diversity of hardware, software and data processing pipelines for capturing fireball events vary between camera networks. This hinders the speed of detecting and triangulating a meteorite-dropping fireball event as each fireball requires a bespoke solution to translate the data into the other networks’ format. A consistent method for rapidly transferring and converting the diversity of outputs produced by each network into a standard format that can be read and utilised by each network is required and is critical to facilitate a rapid UK response to fireball events and associated recovery effort. Here we describe the first iteration of a new code that will enable rapid conversion of data outputs from both video and still image camera networks. The code provides an effective bridging solution, while the ultimate aim is to agree and implement a globally accepted standardised format for fireball observations that can be readily transferred and utilised between camera networks to facilitate meteorite fall recovery. We also describe the logistical issues encountered by UKFAll and the solutions being implemented, including: recruitment of citizen scientists as searchers; conduct and liability issues; and best practice for collection. References Bland, P.A., et al., (2006). Weathering of chondritic meteorites. Meteorites and the early solar system II, 1, 853-867. Borovička J., et al., (2015). Small near‐Earth asteroids as a source of meteorites. In Asteroids IV, edited by Michel P., DeMeo F.E., and Bottke W.F. Tucson, Arizona: University of Arizona Press. pp. 257–280. Bowden, A.J. 2006. “Meteorite provenance and the asteroid connection”. In The history of meteoritics and key meteorite collections; fireballs, falls and finds, Edited by: G.J.H., McCall, A.J., Bowden and R.J., Howarth. Vol. 256, 379–403. Geological Society, London, Special Publications. Chan, Q.H., et al., (2018). Organic matter in extraterrestrial water-bearing salt crystals. Science advances, 4(1), eaao3521. Devillepoix, H.A., et al., (2018). The dingle dell meteorite: a halloween treat from the main belt. Meteoritics & Planetary Science, 53(10), 2212-2227. Devillepoix, H.A.R., et al., (2020). A Global Fireball Observatory. arXiv preprint arXiv:2004.01069. Howie, R.M., et al., (2017). How to build a continental scale fireball camera network. Experimental Astronomy, 43(3), 237-266. Hutchison, R., et al., (1991). The L6 chondrite fall at Glatton, England, 1991 May 5. Meteoritics, 26, 349. MetBull (2020), The meteoritical bulletin database. URL: https://www.lpi.usra.edu/meteor/metbull.php Spurný P., et al., (2014). Reanalysis of the Benešov bolide and recovery of polymict breccia meteorites—Old mystery solved after 20 years. Astronomy & Astrophysics 570:A39.

Recent global crises have created a significant increase in the number of people leaving their countries. Distress experienced by these refugees often leads to posttraumatic stress disorder and depression and can also result in psychotic disorders, substance abuse, and interpersonal violence. The World Health Organization leads the organizing of refugee services as part of a larger initiative to provide mental health services to citizens in low- and middle-income countries. The World Health Organization has identified challenges in providing care, including a provider shortage, issues with how refugees access and receive care and a lack of uniformity in mental health services. By applying the values and systemic orientation of the profession, family therapists can address some of the challenges in treating mental health concerns of these at-risk populations.

Non-classical MHC class I molecule HLA-E is the ligand for CD94/NKG2 NK cell receptors. Surface expression of HLA-E requires binding of specific HLA class I leader sequences. The uterine mucosa in early pregnancy (decidua) is infiltrated by large numbers of NK cells, which are closely associated with placental trophoblast cells. In this study we demonstrate that trophoblast cells express HLA-E on their cell surface in addition to the previously reported expression of HLA-G and HLA-C. Furthermore, we show that the vast majority of decidual NK cells bind to HLA-E tetrameric complexes and this binding is inhibited by mAb to CD94. Thus, recognition of fetal HLA-E by decidual NK cells may play a key role in regulation of placentation. The functional consequences of decidual NK cell interaction were investigated in cytotoxicity assays using polyclonal decidual NK cells. The overall effect of CD94/NKG2 interaction with HLA-E is inhibition of cytotoxicity by decidual NK cells. However, since decidual NK cells are unable to kill trophoblast even in the presence of mAb to MHC class I molecules and NK cell receptors, HLA-E interaction with CD94/NKG2 receptors may regulate other functions besides cytolysis during implantation.

This article establishes that the suffering of the other represents a serious philosophical and ethical problem in Beauvoir's first post–World War II novel. In fact, the other's suffering poses such a complex problem in Le sang des autres particularly because Beauvoir depicts her characters’ world as a kind of Mitsein, which is Heidegger's word to describe how our lives necessarily intertwine with and envelop the lives of others while still allowing for the existential experience of separation. In the novel, the main characters’ potential responses to the other's suffering—quietism, indifference, charity, and empathy—fail according to the novel's existentialist ethical framework because of the ways these responses deny the fundamental ambiguity of Beauvoirian Mitsein. Only in accepting separation and connection as codependent ethical values do the characters find an ethically palatable response to the other's suffering at the end of the novel.

Objectives Aerial transport of injured patients in rural Southeastern Ecuador is provided by humanitarian organizations with no medical personnel or assistance. We sought to evaluate the feasibility and usefulness of a tailored aeromedical transport (AMT) course for nonmedical personnel (pilot and technicians) in the jungles of Ecuador, where there are no formal medical crew members. Methods Fixed-wing aeromedical flights in the Amazon province of Morona Santiago were analyzed to delineate the injury patterns (IP) and reason for transport (RFT). An 8-hour didactic and hands-on AMTC course based on IP and RFT was developed and administered by the Virginia Commonwealth University (VCU) International trauma system development program (ITSDP) and VCU Life Evac with extensive experience in aeromedical education and training. Pre- and post-test course evaluation was used to assess the medical background and knowledge retention of the participants. Results A total of 5,716 fixed-wing aeromedical transports between Jan 2003 and Dec 2005 were analyzed. The course was developed based on 1176 (20%) RFT resulting from traumatic injuries. Course structure based on identified IP included 4 didactic lectures and hands-on skill training in aerial physiology, airway management, bleeding control, shock, musculoskeletal injuries, immobilization and patient transport. Fifteen students (4 pilots, 4 engineers, 2 physicians, 4 aerial staff and 1 flight operator) participated in the course. Pre- and post-test evaluations demonstrated significant improvement in knowledge from 53% (average 10.53, STD 1.6) to 73% (average 14.53, STD 2.13) p-value < 0.0001). Critical deficiencies in information uptake were identified in airway management and flight physiology Conclusion A tailored AMTC may serve as the first step toward the development of a regionally specific aeromedical transport service. Long-term follow-up is needed to evaluate the real impact of this intervention in terms of morbidity and mortality. How to cite this article Aboutanos MB, Mora FE, Nicholson B, Lovelady J, Dhindsa H, Mata LV, Kleiman D, Chin T, King A, Ivatury RR. Trauma Course for an Aerial Medical Transport System in the Amazon Rainforest of Ecuador. Panam J Trauma Critical Care Emerg Surg 2012;1(1):1-5.

This article begins by asking if the project to write a philosophical novel is not inherently flawed; it would seem that the novelist must either write an ambiguous text, which would not create a strong enough argument to count as philosophy, or she must write a text with a clear argument, which would not be ambiguous enough to count as good fiction. The only other option available would be to exemplify a preexisting abstract philosophical system in the concrete literary world. To move beyond such an impasse, this article turns to the work of Simone de Beauvoir. Beauvoir's unique aesthetic theory in “Literature and Metaphysics” envisions philosophy as an integral part of the literary text and sees the novel not as an argument but as something called a “philosophical appeal” (Beauvoir 2004b). In her first novel, She Came to Stay, such a concept of the philosophical novel allows Beauvoir to make an original contribution to the philosophical tradition—one in which Beauvoir rethinks the problem of solipsism—while still creating a stunning literary work (Beauvoir 1954). A study of the theory and the novel together thus provides a solid understanding of what philosophers stand to gain from the philosophical novel.

Most popular discussions of varieties of English in Appalachia (USA) focus only on vernacular dialect features, suggesting that these hallmark characteristics are common for ‘true’ mountain folk (Dial, 1972). Naturally, the reality of the dialects in this region is more complex and subdued than the stereotype. While traditional features, such as a-prefixing (e.g. she is a-working), have played a role in the region, most stereotypical, Appalachian dialect features are fading from usage today (Hazen, 2006). Appalachia is a long region divided into numerous sections. Depending on the sources consulted, the regional divisions are quite staggering in their differences. For some, the region of Appalachia can stretch as far north as New York and as far south as Mississippi, including parts of 13 states (Appalachian Regional Commission). Other definitions limit the geography to a much smaller range (Wolfram & Christian, 1976). Aware of this problem, we have chosen to focus on one region universally accepted as part of Appalachia: West Virginia. Geographically, the state fits entirely within the boundaries of all definitions of the region. Likewise, West Virginia also fits the socio-economic profile most commonly associated with Appalachia. To provide the most comprehensive picture possible, we present a brief overview of English in West Virginia, followed by an empirical examination of 10 dialect features. The import of this empirical investigation is that the West Virginia vernacular of the twenty-first century has changed from its roots at the beginning of the twentieth century.

The primary objectives were to describe the rate of repeat surgery for stress urinary incontinence (SUI) after release of an obstructing synthetic mid-urethral sling (MUS) and to evaluate the effect of time from sling placement to sling release on repeat surgery rates. The secondary objective was to assess rates of recurrent and persistent SUI.This is a retrospective review of women who underwent synthetic MUS release (incision or excision of segment of sling) from 2005-2013. SUI rates and repeat surgery were ascertained by patient report and urinary distress inventory (UDI-6) questionnaire responses. Data analysis included descriptive statistics and multivariable logistic regression analysis.107 patients were included. Median time to sling release was 22 months (IQR 5-49 months). 43.2% were transobturator slings. 15/107 patients (14%) underwent repeat surgery for SUI. On multivariable analysis, women were significantly less likely to undergo repeat surgery for SUI when sling release was performed24 months after initial sling surgery (OR 0.12, 95% CI 0.02-0.85, P = 0.03) compared to release within 3 months. 49% and 77% reported recurrent and persistent SUI after sling release, of which 83% were significantly bothered.The repeat surgery rate for SUI was 14%. The rate of recurrent SUI was 49%. Most of these women were significantly bothered. On multivariate analysis, longer interval to sling release was associated with decreased likelihood of repeat surgery for SUI. The reason for a low repeat surgery rate for SUI despite a high rate of bothersome SUI should be explored in future studies. Neurourol. Urodynam. 36:349-353, 2017. © 2015 Wiley Periodicals, Inc.

Functional PRL receptors are expressed in the human endometrium during the secretory phase of the menstrual cycle in which PRL stimulates tyrosine phosphorylation of Janus kinase 2 and STAT (signal transducer and activator of transcription) 1 and 5. In this study, we investigated the effect of PRL on the MAPK/ERK pathway in the human endometrium. Human endometrial tissue was collected during the mid to late secretory phase of the menstrual cycle. Western blot analysis performed on proteins, extracted after up to 30 min culture with PRL, demonstrated rapid tyrosine and threonine phosphorylation of ERK 1 and 2 MAPKs. The phosphorylation of ERK, in response to PRL, was localized by immunohistochemistry to glandular epithelial cells and a subset of stromal cells. Using immunofluorescence histochemistry, PRL-induced phosphorylation of ERK in the stromal compartment was localized to the uterine-specific CD56(+) natural killer (NK) cells. We have demonstrated that the PRL receptor is expressed in uterine CD56(+) NK cells in situ by immunofluorescence and in purified decidual CD56(+) NK cells by RT-PCR and Western blotting analysis. We have further demonstrated phosphorylation of ERK 1 and 2 in cultures of purified uterine CD56(+) NK cells, in response to PRL. Our data demonstrate that PRL stimulates the ERK pathway in multiple cellular compartments of the human endometrium and identify uterine CD56(+) NK cells as novel PRL target cells.

Background Chagas disease is a vector-borne parasitic disease of major public health importance. Current prevention efforts are based on triatomine vector control to reduce transmission to humans. Success of vector control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to improved vector control strategies in the Yucatan peninsula, Mexico. Methodology/principal findings We employed a sequence of qualitative and quantitative research methods to investigate knowledge, attitudes and practices surrounding Chagas disease, triatomines and vector control in three rural communities. Our combined data show that community members are well aware of triatomines and are knowledgeable about their habits. However, most have a limited understanding of the transmission dynamics and clinical manifestations of Chagas disease. While triatomine control is not a priority for community members, they frequently use domestic insecticide products including insecticide spray, mosquito coils and plug-in repellents. Families spend about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable, in spite of a cost comparable to the average annual spending on insecticide products. Conclusion/Significance Further education campaigns and possibly financing schemes may lead families to redirect their current vector control spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control., Author Summary Chagas disease is an important parasitic disease transmitted by triatomine bugs. Current prevention efforts are based on eliminating triatomines from homes to reduce disease transmission to humans. However, the success of these control interventions depends on their acceptability and value to affected communities. We aimed to identify opportunities for and barriers to triatomine control strategies in the Yucatan peninsula, Mexico. We used a sequence of group discussion, interviews, and a survey to investigate the perception and knowledge of communities on Chagas disease and triatomines in three villages from the Yucatan peninsula, Mexico. Inhabitants are rather familiar with triatomine bugs, but do not associate well these bugs with Chagas disease and its clinical manifestations. Mosquito rather than triatomine control is a common preoccupation, and households frequently use insecticide spray, mosquito coils and plug-in repellents, spending about $32 US per year on these products. Alternative methods such as yard cleaning and window screens are perceived as desirable and potentially more effective. Screens are nonetheless described as unaffordable. The promotion of education campaigns and possibly financing schemes could help families to redirect their current spending from insecticide products to window screens. Also, synergism with mosquito control efforts should be further explored to motivate community involvement and ensure sustainability of Chagas disease vector control.

Because half its genes are inherited from the father, the embryo during pregnancy has been frequently compared to an allograft transplanted into the maternal uterus. The question why the embryo is, therefore, not rejected by the mother's immune response in the same way as other allografts has still not been satisfactorily answered. Recent investigations indicate that this analogy may not be as close as it initially appears. One major difference is the expression of an unusual combination of HLA class I molecules by the placental trophoblast cells which invade into uterine decidua during implantation. Furthermore, the lymphoid population in the uterus potentially capable of interacting with these trophoblast HLA class I antigens also appears to be unique. These observations have led to the suggestion that implantation might utilise a novel immune system which is different to that seen in clinical transplantation immunology. Much research effort is now directed towards the elucidation of the mechanisms involved and the outcome of this interaction because this is likely to be how implantation is controlled.

Genomic imprinting is the phenomenon whereby mono-allelic expression of certain genes occurs depending on their parental origin. The observation that imprinting only occurs in placental mammals has led to the suggestion that it may play a role in this form of reproduction. In the present study we have investigated the pattern of expression of the human PEG3 gene in the early to term placenta, as well as the uterus and ovary, using RT-PCR, northern blot and in situ hybridization. A comparison is made with the expression of Peg3 in the mouse by histochemical staining in betageo knock out mice. We have demonstrated high levels of PEG3 in the human placenta and have localized the signal to the layer of villous cytotrophoblast cells. In contrast, the pattern of expression of Peg3 in the mouse placenta is less restricted, the message being present in all trophoblast populations. Thus, expression of PEG3/Peg3 in the human and mouse placenta is not directly comparable. We have also detected PEG3 message in the ovarian stroma. We have sequenced the human PEG3 gene from exon 3 to exon 9. By utilizing a polymorphism detected in exon 9, we have established that only the paternal allele is expressed in human placenta. Human PEG3 is therefore maternally imprinted as in mouse.

Angiogenesis is essential for endometrial growth and repair, and disruption of this process may lead to common disorders of women, including menorrhagia and endometriosis. In pregnancy, failure of the endometrial spiral arterioles to undergo remodeling leads to preeclampsia. Here we report that in addition to vascular endothelial growth factor A (VEGF-A), human endometrium expresses messenger ribonucleic acids (mRNAs) encoding VEGF-C, placenta growth factor (PlGF), the angiopoietins, angiopoietin 1 (Ang1) and Ang2, and the receptors VEGFR-3 (Flt-4), Tie 1, and Tie 2. Levels of VEGF-C, PlGF, and Tie 2 changed during the menstrual cycle. Intense hybridization for VEGF-C and PlGF mRNAs was found in uterine nature killer cells in secretory phase endometrium and for Ang2 mRNA in the same cells in the late secretory phase. Interleukin-2 (IL-2) and IL-15 up-regulated VEGF-C, but not PlGF or Ang2, mRNA levels in isolated NK cells. Conditioned medium from decidual NK cells did not induce human umbilical vein endothelial cell apoptosis. These results indicate that human endometrium expresses a wide range of angiogenic growth factors and that uterine nature killer cells may play an important role in the abnormal endometrial angiogenesis that underlies a range of disorders affecting women.

During implantation, the uterine decidua is invaded by extravillous trophoblast (EVT) cells whose function is to destroy the walls of the uterine spiral arteries in order to provide an adequate blood flow to the fetus. These EVT cells express an unusual combination of HLA class I molecules-HLA-C, HLA-E and HLA-G. The decidua is infiltrated by a population of natural killer (NK) cells with a distinctive phenotype of CD56(bright)CD16(-)CD3(-). These cells are particularly numerous in the decidua basalis at the implantation site where they come into close contact with invading EVT cells. These NK cells express a variety of receptors (CD94/NKG2, KIR and ILT) which are known to recognize HLA class I molecules. We believe that interaction between these NK cells and EVT cells provides the controlling influence for implantation.

In this paper definitive evidence that the classical class I product, HLA-C, is expressed on the surface of normal trophoblast cells is provided. HLA-C transcripts were sequenced from cDNA isolated from first trimester trophoblast cells obtained by flow cytometric sorting. Both paternal and maternal alleles were transcribed. HLA-C proteins were demonstrated by biochemical analysis and found on the cell surface in association with beta(2)-microglobulin. Upregulation of cell surface HLA-C but not HLA-G expression after interferon (IFN)-gamma treatment was demonstrated by flow cytometric analysis. Immunohistology has confirmed HLA-C is expressed by all extravillous subpopulations in vivo. The question of whether trophoblast HLA-C molecules interact with decidual NK cells expressing killer Ig-like receptors (KIR) has also been addressed. Our results demonstrate that extravillous trophoblast expresses at least two HLA class I molecules, HLA-G and HLA-C on the cell surface.

The natural killer (NK) cells that are present in the uterine mucosa (decidua) during early pregnancy have a distinctive phenotype, CD56(bright) CD16(-). These cells have previously been shown to proliferate and be activated by interleukin (IL)-2. However, IL-2 is absent from the decidua and placenta, and we have therefore investigated whether IL-15 is present in the uterus and can act on decidual NK cells. Both IL-15 mRNA and protein were found in a variety of cells but particularly in decidual macrophages. IL-15 induced a proliferative response in decidual NK cells that was blocked by anti-IL-15 and was augmented by stem cell factor. The cytolytic activity of decidual NK cells against K562 was augmented. Interestingly, in contrast to IL-2, although activation with IL-15 resulted in some killing of JEG-3 choriocarcinoma cells, normal trophoblast cells remained resistant to lysis. These findings suggest that IL-15 is a candidate cytokine responsible for NK cell proliferation in vivo in the progesterone-dominated secretory endometrium and early decidua.

The transformation of endometrium into decidua is an essential feature of normal implantation and pregnancy. There is a close association with an unusual leukocyte population, uterine natural killer (NK) cells, and onset of decidualization. These uterine NK cells are seen in close contact with stromal cells ultrastructurally and are also seen encircling vessels and glands. The possibility that uterine NK cells in the late secretory phase and in early decidua may be important in initiating and maintaining decidualization is raised. In contrast, the death of uterine NK cells could be an early event in the onset of endometrial breakdown at menstruation. The period between implantation and menstruation (7-14 days after luteinizing hormone surge) is the time when implantation is known to be particularly vulnerable. In this review, the possibility that uterine leukocytes might influence the critical decision that the mid- to late secretory endometrium must make either to decidualize or to undergo menstruation is explored.

The immunological relationship beween the mammalian fetus and its mother during pregnancy has been considered similar to that between a transplanted allograft and its recipient ever since Medawar (1953) first proposed the concept of the ‘fetus as an allograft’ in the early 1950s. Based on this analogy, it has been assumed that implantation of the fetal placenta in the uterus would be controlled similarly by a maternal immune response mediated by T-cells recognizing paternally-derived alloantigens expressed by the placenta. Surprisingly, recent evidence suggests that implantation might involve predominantly a novel allogeneic recognition system based on natural killer cells rather than T-cells (Loke & King, 1995). The cellular and molecular basis of this local immune interaction between the fetal placenta and maternal uterus is now the focus of intense research interest. Since aberrant implantation can cause a variety of clinical problems, including miscarriage, intrauterine growth retardation and pre-eclampsia, an understanding of the immunological mechanism by which this process is controlled could lead to the development of regimens to improve fetal growth and development.

Mice in which the gene that encodes the receptor (R) for leukemia inhibitory factor (LIF) has been deleted show abnormal growth and development of the placenta. This indicates that LIF plays an important role in placental development. The expression of LIF-R and LIF was examined in human trophoblast and decidua using in situ hybridization and immunocytochemistry. LIF-R mRNA and immunoreactivity was localized in villous and extravillous trophoblast throughout pregnancy, and in endothelial cells of the fetal villi. Strong expression of mRNA encoding LIF was detected in decidual leukocytes, which are abundant at the implantation site. Extravillous trophoblast, which invades the maternal decidua, therefore expresses LIF-R as it moves past decidual leukocytes, which express LIF mRNA. The effect of LIF on cultured human trophoblast was examined in vitro. Recombinant human LIF had no effect on [3H]thymidine incorporation by purified extravillous trophoblast, nor on expression of integrins alpha1, alpha5, or beta1 by isolated trophoblast. These results identify fetal endothelial cells and all cells of the trophoblast lineage as targets for the action of LIF in human placenta. Although its effects on trophoblast are not yet clear, LIF appears to mediate interactions between maternal decidual leukocytes and invading trophoblast. LIF may also play a critical role in controlling angiogenesis in the placental villi, since human fetal endothelial cells express LIF-R, and mice lacking a functional LIF receptor gene show altered vascular development in the placenta.

There is considerable interest in human HLA-G arising from the observation that it is expressed selectively on the surface of extravillous trophoblast, the fetal cell population directly in contact with the mother. We investigated several aspects of the molecular biology of this unusual molecule. Limited polymorphism at the nucleotide level, and even more restricted variation at the amino acid level, was found in our Caucasian population. A further unusual aspect of HLA-G is the occurrence of alternatively spliced mRNAs. Spliced messages that could give rise to either membrane-bound or soluble proteins have been reported and six of these alternative forms were detected in all first trimester and term placentae, highly purified villous and extravillous trophoblast and the cell lines, JEG-3 and 221-G. An additional novel splice variant involving loss of part of the 3′-untranslated region was observed with two alleles. Using a sensitive RNase protection assay higher levels of the membrane-bound RNAs as compared to the soluble forms were detected in first trimester and term placentae as well as in JEG-3. Contrary to previous findings our term samples taken from the maternal aspect showed higher levels of both mRNA species when compared to first trimester placenta. The question of imprinting was addressed through the detection of heterozygotes both in placental tissue and, more tellingly, in the purified trophoblast cells. There was no evidence of imprinting. In addition we did not find mRNA for HLA-G in human two to eight-cell embryos or in blastocyst or in sperm samples1.

During the luteal phase and the early months of pregnancy, there is a dense mucosal infiltration of CD56+ natural killer (NK) cells. These uterine NK cells have a phenotype (CD56bright, CD16-, mCD3-) which distinguishes them from peripheral blood NK cells (CD56dim, CD16bright, mCD3-). The uterine NK cells are in close association with extravillous trophoblast (EVT) cells which infiltrate into the decidua and maternal spiral arteries. This subpopulation of trophoblast expresses two human leukocyte antigen (HLA) class I molecules, HLA-G and HLA-C. Circulating NK cells express receptors for HLA class I molecules. We have recently found evidence that similar receptors are present on decidual NK cells belonging to both the Killer Inhibitory Receptor (KIR) and CD94 families. The repertoire of NK receptors expressed varies between different women. The findings indicate that decidual NK cells do have receptors for trophoblast HLA class I molecules. Experiments are underway to determine the effects of this interaction on NK cell function.

Recent research on the relationship between borderline personality disorder (BPD) and suicidal behavior is reviewed. Risk factors for attempted and completed suicide as well as the effect of the comorbidity of BPD with other Axis I and II disorders are considered. Explanations for suicidality in BPD are discussed. General assessment strategies are offered, along with treatment recommendations. Specifically, research has shown that borderline patients improve in the long-term, decreasing in suicidality, self-destructiveness, and interpersonal maladjustment, if survival is effectively managed during the turbulent years of youth. Clinical lore at times can lead clinicians to disregard the danger of suicide completion among chronically parasuicidal patients, which can prevent effective intervention during suicidal crises and result in unfortunate outcomes.

In early pregnancy the uterine mucosa, the decidua, is infiltrated by numerous CD56bright, CD16- natural killer (NK) cells. In this paper we have shown that unlike adult peripheral blood NK cells these uterine NK cells express cytoplasmic CD3 and CD3 zeta, but CD3 gamma and CD3 delta were not found in the majority of cells. In contrast to previous reports, there was no evidence of RAG-1 nor RAG-2 expression in decidual NK cells. These findings have implications for the ontogeny and development of decidual NK cells.

Summary In this review the problem of intrauterine infection of the fetus has been discussed in the light of knowledge gained from studying the immunology of maternal-fetal interactions. The non-classical HLA class I molecule HLA-G is expressed exclusively by extravillous trophoblast cells and has been proposed to play a role in protecting the fetus from maternal infection. However, the anatomical site of HLA-G expression, the diminishing expression of HLA-G throughout gestation, the lack of HLA-G reactive T cells and the minimal polymorphism would argue against this role. It is also difficult to ascribe a function for the endometrial and decidual natural killer (NK) cells in combating infectious diseases. These NK cells have similar characteristics to NK cells circulating in adult blood, which are known to be important in the defense against viral infections. However, since uterine NK cells are only present in large numbers in the progesterone stimulated uterine mucosa and are sparse in the proliferative phase of the normal menstrual cycle, it is difficult to envisage how these cells can be a vital component of the uterine mucosal defense. Systemic immune responses during pregnancy appear to be deviated toward Th2 away from Th1. This phenomenon will affect the severity of disease and transplacental transmission of infection caused by intracellular and extracellular pathogens. Transfer of immunoglobulins across the placenta is via a specific receptor, FcRn, which structurally resembles an HLA class I molecule. As well as transfering protective antibodies to the fetus, potentially harmful auto-antibodies may also cross. However, some alloantibodies directed to paternally encoded antigens can be removed by placental cells, giving rise to the idea of the placenta acting as an “immunological sponge”. In conclusion, it is clear that a study of the immunology of the fetal-maternal interaction could provide a new perspective on intrauterine infection.

The establishment of the human placenta in early pregnancy is characterized by the presence of large numbers of natural killer (NK) cells within the maternal decidua in close proximity to the fetally-derived invading extravillous trophoblast which expresses at least two HLA class I molecules, HLA-G and HLA-C. These NK cells have an unusual phenotype, CD56(bright) CD16, distinguishing them from adult peripheral blood NK cells. They may control key events in trophoblast migration and therefore placentation. Human NK cells in peripheral blood express receptors for polymorphic HLA class I molecules. This family of receptors, known as killer cell inhibitory receptors (KIR), are expressed on overlapping subsets of NK cells to give an NK cell repertoire which differs between individuals. Using a panel of monoclonal antibodies to several members of the KIR family and analysis by flow cytometry, we have found that KIR are expressed by decidual NK cells. There is variation in both the percentage of cells expressing a particular receptor and the density of receptor expression between decidual NK cells from different individuals. Comparison of NK cells from decidua and peripheral blood of the same individual showed that NK cells from these two different locations express different repertoires of KIR. Receptors are present in individuals who do not possess the relevant class I ligand, raising the possibility that these NK receptors may be involved in recognition of the allogeneic fetus by the mother at the implantation site.