Using Advanced Cell Culture Techniques to Differentiate Pluripotent Stem Cells and Recreate Tissue Structures Representative of Teratoma Xenografts

Various methods are currently used to investigate human tissue differentiation, including human embryo culture and studies utilising pluripotent stem cells (PSCs) such as in vitro embryoid body formation and in vivo teratoma assays. Each method has its own distinct advantages, yet many are limited due to being unable to achieve the complexity and maturity of tissue structures observed in the developed human. The teratoma xenograft assay allows maturation of more complex tissue derivatives, but this method has ethical issues surrounding animal usage and significant protocol variation. In this study, we have combined three-dimensional (3D) in vitro cell technologies including the common technique of embryoid body (EB) formation with a novel porous scaffold membrane, in order to prolong cell viability and extend the differentiation of PSC derived EBs. This approach enables the formation of more complex morphologically identifiable 3D tissue structures representative of all three primary germ layers. Preliminary in vitro work with the human embryonal carcinoma line TERA2.SP12 demonstrated improved EB viability and enhanced tissue structure formation, comparable to teratocarcinoma xenografts derived in vivo from the same cell line. This is thought to be due to reduced diffusion distances as the shape of the spherical EB transforms and flattens, allowing for improved nutritional/oxygen support to the developing structures over extended periods. Further work with EBs derived from murine embryonic stem cells demonstrated that the formation of a wide range of complex, recognisable tissue structures could be achieved within 2-3 weeks of culture. Rudimentary tissue structures from all three germ layers were present, including epidermal, cartilage and epithelial tissues, again, strongly resembling tissue structure of teratoma xenografts of the same cell line. Proof of concept work with EBs derived from the human embryonic stem cell line H9 also showed the ability to form complex tissue structures within this system. This novel yet simple model offers a controllable, reproducible method to achieve complex tissue formation in vitro. It has the potential to be used to study human developmental processes, as well as offering an animal free alternative method to the teratoma assay to assess the developmental potential of novel stem cell lines

Human Clostridium difficile infection caused by a livestock-associated PCR ribotype 237 strain in Western Australia

Introduction: Clostridium difficile infection (CDI) is a significant gastrointestinal disease in the developed world and increasingly recognised as a zoonotic infection. In North America and Europe, the PCR ribotype (RT) 078 strain of C. difficile is commonly found in production animals and as a cause of disease in humans although proof of transmission from animals is lacking. This strain is absent in Australian livestock. We report a case of human CDI caused by a strain of C. difficile belonging to known Australian livestock-associated RT 237. Case presentation: A young male was admitted for multiple trauma following a motor vehicle accident and placed on piperacillin/tazobactam for pneumonia. After 4 days of treatment, he developed symptoms of CDI, which was confirmed in the laboratory. His symptoms resolved after 6 days of intravenous metronidazole. The strain of C. difficile isolated was identified as RT 237, an unusual RT previously found in with several Western Australia piggeries. Conclusion: This case of CDI caused by an unusual livestock-associated C. difficile RT 237 supports the hypothesis of zoonotic transmission. The case highlights the potential of livestock to act as reservoir for C. difficile and the need for continued surveillance of CDI in both human and animal populations

Remote system for detection of low-levels of methane based on photonic crystal fibres and wavelength modulation spectroscopy

In this work we described an optical fibre sensing system for detecting low levels of methane. The properties of hollow-core photonic crystal fibres are explored to have a sensing head with favourable characteristics for gas sensing, particularly in what concerns intrinsic readout sensitivity and gas diffusion time in the sensing structure. The sensor interrogation was performed applying the Wavelength Modulation Spectroscopy technique, and a portable measurement unit was developed with performance suitable for remote detection of low levels of methane. This portable system has the capacity to simultaneously interrogate four remote photonic crystal fibre sensing heads. Copyright © 2009 J. P. Carvalho et al

Influence of the detector's temperature on the quantum Zeno effect

In this paper we study the quantum Zeno effect using the irreversible model of the measurement. The detector is modeled as a harmonic oscillator interacting with the environment. The oscillator is subjected to the force, proportional to the energy of the measured system. We use the Lindblad-type master equation to model the interaction with the environment. The influence of the detector's temperature on the quantum Zeno effect is obtained. It is shown that the quantum Zeno effect becomes stronger (the jump probability decreases) when the detector's temperature increases

Quantum Anti-Zeno Effect

We demonstrate that near threshold decay processes may be accelerated by repeated measurements. Examples include near threshold photodetachment of an electron from a negative ion, and spontaneous emission in a cavity close to the cutoff frequency, or in a photon band gap material.Comment: 4 pages, 3 figure

Modeling magnetospheric fields in the Jupiter system

The various processes which generate magnetic fields within the Jupiter system are exemplary for a large class of similar processes occurring at other planets in the solar system, but also around extrasolar planets. Jupiter's large internal dynamo magnetic field generates a gigantic magnetosphere, which is strongly rotational driven and possesses large plasma sources located deeply within the magnetosphere. The combination of the latter two effects is the primary reason for Jupiter's main auroral ovals. Jupiter's moon Ganymede is the only known moon with an intrinsic dynamo magnetic field, which generates a mini-magnetosphere located within Jupiter's larger magnetosphere including two auroral ovals. Ganymede's magnetosphere is qualitatively different compared to the one from Jupiter. It possesses no bow shock but develops Alfv\'en wings similar to most of the extrasolar planets which orbit their host stars within 0.1 AU. New numerical models of Jupiter's and Ganymede's magnetospheres presented here provide quantitative insight into the processes that maintain these magnetospheres. Jupiter's magnetospheric field is approximately time-periodic at the locations of Jupiter's moons and induces secondary magnetic fields in electrically conductive layers such as subsurface oceans. In the case of Ganymede, these secondary magnetic fields influence the oscillation of the location of its auroral ovals. Based on dedicated Hubble Space Telescope observations, an analysis of the amplitudes of the auroral oscillations provides evidence that Ganymede harbors a subsurface ocean. Callisto in contrast does not possess a mini-magnetosphere, but still shows a perturbed magnetic field environment. Callisto's ionosphere and atmospheric UV emission is different compared to the other Galilean satellites as it is primarily been generated by solar photons compared to magnetospheric electrons.Comment: Chapter for Book: Planetary Magnetis

Where’s the “Everyday Black Woman”? An intersectional qualitative analysis of Black Women’s decision-making regarding HIV pre-exposure prophylaxis (PrEP) in Mississippi

Background: Black cisgender women in the U.S. South bear a disproportionate burden of HIV compared to cisgender women in other racial and ethnic groups and in any other part of the US. Critical to decreasing new HIV infections is the improved delivery of pre-exposure prophylaxis (PrEP) for Black cisgender women as it remains underutilized in 2021. Informed by intersectionality, the study sought to characterize the sociostructural influences on Black cisgender women’s deliberations about PrEP within the context of interlocking systems of oppression including racism, sexism, and classism. Methods: Six focus groups were conducted with 37 Black women residing in Jackson, Mississippi. This sample was purposively recruited to include Black cisgender women who were eligible for PrEP but had never received a PrEP prescription. Results: Six themes were identified as concerns during PrEP deliberation among Black women: 1) limited PrEP awareness, 2) low perceived HIV risk, 3) concerns about side effects, 4) concerns about costs, 5) limited marketing, and 6) distrust in the healthcare system. Three themes were identified as facilitators during PrEP deliberations: 1) women’s empowerment and advocacy, 2) need for increased PrEP-specific education, and 3) the positive influence of PrEP-engaged women’s testimonials. Black women shared a limited awareness of PrEP exacerbated by the lack of Black women-specific marketing. Opportunities to support Black women-specific social marketing could increase awareness and knowledge regarding PrEP’s benefits and costs. Black women also shared their concerns about discrimination in healthcare and distrust, but they felt that these barriers may be addressed by patient testimonials from PrEP-engaged Black women, empowerment strategies, and directly addressing provider biases. Conclusions: An effective response to PrEP implementation among Black women in the South requires developing programs to center the needs of Black women and carry out active strategies that prioritize peer advocacy while reinforcing positive and mitigating negative influences from broader social and historical contexts

“PrEP’s just to secure you like insurance”: a qualitative study on HIV pre-exposure prophylaxis (PrEP) adherence and retention among black cisgender women in Mississippi

Background: Pre-exposure prophylaxis (PrEP) has the potential to reduce transmission of HIV among Black cisgender women in the Southern United States (U.S.); however, national data suggests that PrEP initiation is lowest in the South and among Black women compared to other U.S. regions and white women. This study applied intersectionality and PrEP multilevel resilience frameworks to assess how socio-structural and clinical contexts shaped PrEP persistence among Black cisgender women in Mississippi. Methods: Semi-structured interviews were conducted with eight Black cisgender women in Jackson, Mississippi. This sample was purposively recruited to include PrEP-initiated Black cisgender women. Results: Six themes identified that shaped PrEP care among Black cisgender women: (1) internal assets, (2) sole responsibility to HIV prevention, (3) added protection in HIV serodifferent relationships, (4) financial issues, (5) trust and distrust in the medical system, and (6) side effects. Black cisgender women reported that PrEP persistence increased control over their sexual health, reduced anxiety about HIV, and promoted self-care. Black cisgender women also indicated that medication assistance programs increased PrEP affordability resulting in continued persistence. Conclusions: In addition to preventing HIV, PrEP may yield secondary positive impacts on the health and relationships of Black cisgender women. However, very few Black cisgender women in the South are using PrEP given intersectional barriers and thus necessitates adaptive strategies to support PrEP initiation and persistence. Efforts aimed at increasing the coverage of PrEP among Black cisgender women should consider implementation strategies responsive to lived realities of Black women

Conducting clinical genomics research during the COVID-19 pandemic: Lessons learned from the CSER consortium experience

Clinical research studies have navigated many changes throughout the COVID-19 pandemic. We sought to describe the pandemic′s impact on research operations in the context of a clinical genomics research consortium that aimed to enroll a majority of participants from underrepresented populations. We interviewed (July to November 2020) and surveyed (May to August 2021) representatives of six projects in the Clinical Sequencing Evidence-Generating Research (CSER) consortium, which studies the implementation of genome sequencing in the clinical care of patients from populations that are underrepresented in genomics research or are medically underserved. Questions focused on COVID′s impact on participant recruitment, enrollment, and engagement, and the transition to teleresearch. Responses were combined and thematically analyzed. Projects described factors at the project, institutional, and community levels that affected their experiences. Project factors included the project′s progress at the pandemic′s onset, the urgency of in-person clinical care for the disease being studied, and the degree to which teleresearch procedures were already incorporated. Institutional and community factors included institutional guidance for research and clinical care and the burden of COVID on the local community. Overall, being responsive to community experiences and values was essential to how CSER navigated evolving challenges during the COVID-19 pandemic

Patterns in random walks and Brownian motion

We ask if it is possible to find some particular continuous paths of unit length in linear Brownian motion. Beginning with a discrete version of the problem, we derive the asymptotics of the expected waiting time for several interesting patterns. These suggest corresponding results on the existence/non-existence of continuous paths embedded in Brownian motion. With further effort we are able to prove some of these existence and non-existence results by various stochastic analysis arguments. A list of open problems is presented.Comment: 31 pages, 4 figures. This paper is published at http://link.springer.com/chapter/10.1007/978-3-319-18585-9_