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Background: Adherence challenges with oral tenofovir-based pre-exposure prophylaxis (PrEP) are common. We developed a point-of-care assay to objectively assess tenofovir in urine and conducted a pilot trial examining the impact of counselling informed by use of this urine assay on long-term PrEP adherence., Methods: This randomised trial enrolled women not in serodiscordant partnerships 3 months after PrEP initiation at the Kenya Medical Research Institute to compare standard-of-care adherence counselling versus counselling informed by the urine assay (urine-test counselling group) every 3 months for 12 months. In the standard of care group, urine samples were stored and tested at study end without participant feedback. Here we report the adherence primary outcome of hair concentrations of tenofovir at 12 months as a long-term metric (undetectable levels defined long-term non-adherence), as well as urine concentrations of tenofovir at each visit as a short-term adherence metric and acceptability of the assay assessed by quantitative surveys. Data were analysed by randomisation group. This completed trial was registered with ClinicalTrials.gov (NCT03935464)., Findings: From March 17, 2021 to Jan 18, 2022 we enrolled 49 women in the urine-test counselling group and 51 in the standard of care group; retention was 86 (86%) of 100. Nine (21%) of 42 in the urine-test counselling group had hair samples at 12 months with tenofovir concentrations below the limit of quantification compared with 15 (37%) of 41 in the standard of care group. The relative odds of long-term non-adherence in the standard of care group compared with urine-test counselling were 3·53 (95% CI 1·03-12·03; p=0·044). Pre-intervention, urine tenofovir was detectable in 65% in the urine-test counselling group and 71% in the standard of care group (p=0·68). At 12 months, 31 (72%) of 43 in the intervention group had detectable urine tenofovir compared with 19 (45%) of 42 in the standard of care group (p=0·0015). 40 (93%) of 43 participants liked the test very much and only one disliked the test. One participant in the standard of care group was withdrawn at the 6-month visit due to HIV seroconversion., Interpretation: A low-cost urine tenofovir assay to inform PrEP counselling resulted in improvement in both short-term and long-term metrics of adherence. This urine tenofovir assay could help to improve long-term PrEP adherence., Funding: National Institute of Allergy and Infectious Diseases and National Institutes of Health., Competing Interests: Declaration of interests MG's Hair Analytical Laboratory co-owns the patent on the antibody directed against tenofovir with Abbott Laboratories. DVG has received consulting fees from Gilead Sciences. Beyond receiving National Institutes of Health grants which provide support to KN's institution, KN has received additional grant funding from the Bill & Melinda Gates Foundation, United States Agency for International Development, and Merck Pharmaceuticals. All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Group-III nitrides have transformed solid-state lighting and are strategically positioned to revolutionize high-power and high-frequency electronics. To drive this development forward, a deep understanding of fundamental material properties, such as charge carrier behavior, is essential and can also unveil new and unforeseen applications. This underscores the necessity for novel characterization tools to study group-III nitride materials and devices. The optical Hall effect (OHE) emerges as a contactless method for exploring the transport and electronic properties of semiconductor materials, simultaneously offering insights into their dielectric function. This non-destructive technique employs spectroscopic ellipsometry at long wavelengths in the presence of a magnetic field and provides quantitative information on the charge carrier density, sign, mobility, and effective mass of individual layers in multilayer structures and bulk materials. In this paper, we explore the use of terahertz (THz) OHE to study the charge carrier properties in group-III nitride heterostructures and bulk material. Examples include graded AlGaN channel high-electron-mobility transistor (HEMT) structures for high-linearity devices, highlighting the different grading profiles and their impact on the two-dimensional electron gas (2DEG) properties. Next, we demonstrate the sensitivity of the THz OHE to distinguish the 2DEG anisotropic mobility parameters in N-polar GaN/AlGaN HEMTs and show that this anisotropy is induced by the step-like surface morphology. Finally, we present the temperature-dependent results on the charge carrier properties of 2DEG and bulk electrons in GaN with a focus on the effective mass parameter and review the effective mass parameters reported in the literature. These studies showcase the capabilities of the THz OHE for advancing the understanding and development of group-III materials and devices.

Background: In 2020, healthcare providers were expected to provide care to individuals with coronavirus disease 2019 (COVID-19), putting them at risk of acquiring COVID-19. The possibility of acquiring poorly understood infectious diseases while providing care may have an impact on the mental health of providers. We conducted a study to explore the effects of COVID-19 on the mental health of healthcare providers., Methods: Between April and August 2021, we conducted in-depth interviews with 60 healthcare providers in the infectious disease unit (IDU) and other units of the hospital (non-IDU). The healthcare providers completed an online self-administered survey form with demographic data (age, sex, average income, and known contact with a COVID-19 patient). We used semi-structured interview guides to understand the healthcare providers' lived experiences of stress, anxiety, depression, and their associated factors. We transcribed the interviews verbatim and coded and analyzed the transcripts to derive thematic concepts related to mental health experiences., Results: The healthcare providers had a median age of 37 years [IQR 20.0-58.0], and 56.7% were female, 30.0% nurses, 18.3% medical doctors, and 11.7% laboratory technologists. The healthcare providers reported increased stress during the pandemic, attributed to the high demand for patient care, changes in social life, and fear of COVID-19 infection. They also reported experiences of anxiety and depression as a result of limited knowledge at the beginning of the pandemic and the perception that "COVID-19 resulted in death". Testing positive for COVID-19, high exposure to COVID-19 risks, and the death of patients and colleagues reportedly affected the healthcare providers' mental health. Additionally, the healthcare providers reported mental health support through debriefing meetings, peer-to-peer support, and psychological counseling, with privacy and confidentiality concerns., Conclusions: Healthcare providers faced mental health issues such as stress and anxiety while taking care of COVID-19 patients. An effective mental health response requires institutional practices that address context-specific challenges such as privacy and confidentiality.

Introduction: Delivery of oral pre-exposure prophylaxis (PrEP) is being scaled up in Africa, but clinic-level barriers including lengthy clinic visits may threaten client continuation on PrEP., Methods: Between January 2020 and January 2022, we conducted a quasi-experimental evaluation of differentiated direct-to-pharmacy PrEP refill visits at four public health HIV clinics in Kenya. Two clinics implemented the intervention package, which included direct-to-pharmacy for PrEP refill, client HIV self-testing (HIVST), client navigator, and pharmacist-led rapid risk assessment and dispensing. Two other clinics with comparable size and client volume served as contemporaneous controls with the usual clinic flow. PrEP continuation was evaluated by visit attendance and pharmacy refill records, and time and motion studies were conducted to determine time spent in the clinics. Dried blood spots were collected to test for tenofovir-diphosphate (TFV-DP) at random visits. We used logistic regression to assess the intervention effect on PrEP continuation and the Wilcoxon rank sum test to assess the effect on clinic time., Results: Overall, 746 clients were enrolled, 366 at control clinics (76 during pre-implementation and 290 during implementation phase), and 380 at direct-to-pharmacy clinics (116 during pre-implementation and 264 during implementation phase). Prior to implementation, the intervention and control clinics were comparable on client characteristics (female: 51% vs. 47%; median age: 33 vs. 33 years) and PrEP continuation (35% vs. 37% at 1 month, and 37% vs. 39% at 3 months). The intervention reduced total time spent at the clinic by 35% (median of 51 minutes at control vs. 33 minutes at intervention clinics; p<0.001), while time spent on HIV testing (20 vs. 20 minutes; p = 0.50) and pharmacy (8 vs. 8 minutes; p = 0.8) was unchanged. PrEP continuation was higher at intervention versus the control clinics: 45% versus 33% at month 1, 34% versus 25% at month 3 and 23% versus 16% at month 6. TFV-DP was detected in 85% (61/72) of samples, similar by the study group (83% vs. 85%)., Conclusions: A client-centred PrEP delivery approach with direct-to-pharmacy PrEP refill visits plus client HIVST significantly reduced clinic visit time by more than one-third and improved PrEP continuation in public health HIV clinics in Kenya., (© 2024 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of International AIDS Society.)

HIV self-testing (HIVST) has the potential to reduce barriers associated with clinic-based preexposure prophylaxis (PrEP) delivery. We conducted a substudy nested in a prospective, pilot implementation study evaluating patient-centered differentiated care services. Clients chose either a blood-based or oral fluid HIVST kit at the first refill visit. Data were abstracted from program files and surveys were administered to clients. We purposively sampled a subset of PrEP clients and their providers to participate in in-depth interviews. We surveyed ( n  = 285). A majority (269/285, 94%) reported HIV risk. Blood-based HIVST was perceived as easy to use (76/140, 54%), and (41/140, 29%) perceived it to be more accurate. Oral fluid-based HIVST was perceived to be easy to use (95/107, 89%), but almost all (106/107, 99%) perceived it as less accurate. HIVST improved privacy, reduced workload, and saved time. HIVST demonstrates the potential to streamline facility-based PrEP care in busy African public health facilities., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Terahertz (THz) technologies provide opportunities ranging from calibration targets for satellites and telescopes to communication devices and biomedical imaging systems. A main component will be broadband THz absorbers with switchability. However, optically switchable materials in THz are scarce and their modulation is mostly available at narrow bandwidths. Realizing materials with large and broadband modulation in absorption or transmission forms a critical challenge. This study demonstrates that conducting polymer-cellulose aerogels can provide modulation of broadband THz light with large modulation range from ≈ 13% to 91% absolute transmission, while maintaining specular reflection loss < -30 dB. The exceptional THz modulation is associated with the anomalous optical conductivity peak of conducting polymers, which enhances the absorption in its oxidized state. The study also demonstrates the possibility to reduce the surface hydrophilicity by simple chemical modifications, and shows that broadband absorption of the aerogels at optical frequencies enables de-frosting by solar-induced heating. These low-cost, aqueous solution-processable, sustainable, and bio-friendly aerogels may find use in next-generation intelligent THz devices., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Few studies have focused on understanding pre-exposure prophylaxis (PrEP) non-initiation among young, high-risk women in sub-Saharan Africa. This study aimed to qualitatively explore why young women in Kenya at high-risk for HIV chose not to enroll in a PrEP adherence trial. We performed 40 semi-structured interviews with young high-risk women assessing concerns about PrEP and/or study participation. We also assessed community-level factors influencing decision-making around PrEP through 10 focus groups involving peers, young men, caregivers, and community leaders. Our qualitative data reflect the complexity of navigating barriers preventing PrEP initiation in settings where taking PrEP may be perceived as immoral behavior. Framed within the context of risk perception, the decision to start PrEP may run counter to the potential risk of losing support from one's community. Our findings suggest that approaches addressing social norms, while de-medicalizing HIV prevention services, are needed to further increase PrEP uptake among young Kenyan women., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Adherence to oral pre-exposure prophylaxis (PrEP) is challenging, and cellular technology offers a promising opportunity for support. However, a recent randomized controlled trial found that SMS reminders did not improve PrEP adherence. We used qualitative methods to explore the trial participants' experiences with the SMS intervention. We conducted serial in-depth interviews with 54 young Kenyan women, using inductive and deductive content analysis . Initially, SMS reminders were highly acceptable. Participants expressed enthusiasm with receiving the reminders because of the coded nature of the SMS reminders; they also helped in 'habit forming' with daily adherence. However, overtime, participants reported growing concerns about privacy, self-efficacy, and responsibility and SMS fatigue. Participants also reported other challenges, including phone loss, poor telephone network, and lack of electricity. Further research to explore if SMS reminders in alternative formats or with different frequency is needed, in addition to identification of alternate adherence support strategies., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Falls are a common complication experienced after a stroke and can cause serious detriments to physical health and social mobility, necessitating a dire need for intervention. Among recent advancements, wearable airbag technology has been designed to detect and mitigate fall impact. However, these devices have not been designed nor validated for the stroke population and thus, may inadequately detect falls in individuals with stroke-related motor impairments. To address this gap, we investigated whether population-specific training data and modeling parameters are required to pre-detect falls in a chronic stroke population., Methods: We collected data from a wearable airbag's inertial measurement units (IMUs) from individuals with (n = 20 stroke) and without (n = 15 control) history of stroke while performing a series of falls (842 falls total) and non-falls (961 non-falls total) in a laboratory setting. A leave-one-subject-out crossvalidation was used to compare the performance of two identical machine learned models (adaptive boosting classifier) trained on cohort-dependent data (control or stroke) to pre-detect falls in the stroke cohort., Results: The average performance of the model trained on stroke data (recall = 0.905, precision = 0.900) had statistically significantly better recall (P = 0.0035) than the model trained on control data (recall = 0.800, precision = 0.944), while precision was not statistically significantly different. Stratifying models trained on specific fall types revealed differences in pre-detecting anterior-posterior (AP) falls (stroke-trained model's F 1 -score was 35% higher, P = 0.019). Using activities of daily living as non-falls training data (compared to near-falls) significantly increased the AUC (Area under the receiver operating characteristic) for classifying AP falls for both models (P < 0.04). Preliminary analysis suggests that users with more severe stroke impairments benefit further from a stroke-trained model. The optimal lead time (time interval pre-impact to detect falls) differed between control- and stroke-trained models., Conclusions: These results demonstrate the importance of population sensitivity, non-falls data, and optimal lead time for machine learned pre-impact fall detection specific to stroke. Existing fall mitigation technologies should be challenged to include data of neurologically impaired individuals in model development to adequately detect falls in other high fall risk populations. Trial registration https://clinicaltrials.gov/ct2/show/NCT05076565 ; Unique Identifier: NCT05076565. Retrospectively registered on 13 October 2021., (© 2022. The Author(s).)

Background: In Kenya and elsewhere in sub-Saharan Africa, young women are disproportionately affected by the HIV epidemic compared to young men. The extent to which young women's self-perceptions about risk of HIV acquisition influence their sexual behaviors and use of HIV prevention methods remains unclear. We therefore conducted a qualitative study to explore these issues among young women enrolled in a pre-exposure prophylaxis (PrEP) trial. Methods: From January 2017 to January 2020, we conducted serial semi-structured in-depth interviews 50 purposively selected young women (18-24 years old) who were participating in the MPYA (Monitoring PrEP for Young Adult women) study-a randomized controlled trial in Thika and Kisumu, Kenya, assessing the impact of SMS reminders on PrEP adherence. Interviews were conducted at three time points (~1 week, 3, and 12 months after initiating PrEP). We used an inductive, content analytic approach to identify key themes related to risk perceptions, sexual behavior, and use of HIV prevention tools. Results: Around the time of enrollment, most of the 50 women interviewed reported being at high risk of HIV because of their own sexual behaviors, such as inconsistent condom use, multiple sexual partners, and transactional sex. Additionally, high risk perception was based on the behavior of their partners, such as refusing to use condoms and being unsure of their partner's HIV status. Young women's perceived risk of HIV acquisition was a key motivator for PrEP initiation and continuation. During PrEP use, participants reported feeling protected and at less risk compared to peers who were not taking PrEP. Some reported no longer using condoms because they were confident that PrEP provided enough protection. Over time, many young women reported reducing risky sexual behaviors because of the regular counseling and HIV testing they received as part of their PrEP services. This lowered risk perception was in most cases accompanied by discontinuation of PrEP. Conclusions: HIV risk perception among young women in Kenya was dynamic and influenced their use of PrEP and condoms over time, suggesting an often-deliberate approach to HIV prevention and sexual health., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ngure, Thuo, Ogello, Kiptinness, Kamolloh, Burns, Mugo, Bukusi, Garrison, Baeten and Haberer.)

Precise manipulation of light-matter interactions has enabled a wide variety of approaches to create bright and vivid structural colors. Techniques utilizing photonic crystals, Fabry-Pérot cavities, plasmonics, or high-refractive-index dielectric metasurfaces have been studied for applications ranging from optical coatings to reflective displays. However, complicated fabrication procedures for sub-wavelength nanostructures, limited active areas, and inherent absence of tunability of these approaches impede their further development toward flexible, large-scale, and switchable devices compatible with facile and cost-effective production. Here, a novel method is presented to generate structural color images based on monochromic conducting polymer films prepared on metallic surfaces via vapor phase polymerization and ultraviolet (UV) light patterning. Varying the UV dose enables synergistic control of both nanoscale film thickness and polymer permittivity, which generates controllable structural colors from violet to red. Together with grayscale photomasks this enables facile fabrication of high-resolution structural color images. Dynamic tuning of colored surfaces and images via electrochemical modulation of the polymer redox state is further demonstrated. The simple structure, facile fabrication, wide color gamut, and dynamic color tuning make this concept competitive for applications like multifunctional displays., (© 2021 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Introduction: Post-abortion clinics located in regions with high HIV burden may ideal locations to integrate counselling and delivery of HIV pre-exposure prophylaxis (PrEP), aligning with normative goals for integrated delivery of HIV and reproductive health care. The objective of this study was to gauge the degree to which Kenyan women seeking care for a pregnancy loss, including induced abortion, are at risk for HIV and whether women would welcome an introduction to PrEP prior to discharge from post-abortion care., Methods: We conducted a mixed-methods study from August 2019 to February 2020 with women ages 15 to 30 recruited sequentially as they were accessing post-abortion care at public and private facilities in Thika and Kisumu, Kenya. Data collection was through a cross-sectional survey and laboratory testing for common sexually transmitted infections (N = 200), and in-depth interviews (N = 30). Descriptive statistics summarize PrEP knowledge and referrals and a multivariable log-link binomial model estimated correlates of receiving a referral for PrEP. Qualitative data were analysed using inductive and deductive approaches., Results: Among 200 HIV-negative women (median age 21.0, interquartile range 19.0 to 22.0), the prevalence of Chlamydia trachomatis was 18.2% and Neisseria gonorrhoeae was 2.0%. Half of the women scored ≥5 on a validated tool that would correspond to an expected HIV incidence of 9.5% per year. Approximately half (55.8%) of women were familiar with PrEP prior to the study and 33.3% received a referral from study staff to a clinic offering PrEP. In qualitative interviews, women expressed interest in accessing PrEP from the gynaecology ward that provided post-abortion care but they preferred alternative locations for PrEP refills., Conclusions: Kenyan women accessing post-abortion care have substantial HIV risk and were favourable about the idea of receiving support to initiate PrEP as part of care offered during post-abortion care. These settings can be integrated into national PrEP programmes as locations providing PrEP referrals and initiation., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

Being able to dynamically shape light at the nanoscale is one of the ultimate goals in nano-optics 1 . Resonant light-matter interaction can be achieved using conventional plasmonics based on metal nanostructures, but their tunability is highly limited due to a fixed permittivity 2 . Materials with switchable states and methods for dynamic control of light-matter interaction at the nanoscale are therefore desired. Here we show that nanodisks of a conductive polymer can support localized surface plasmon resonances in the near-infrared and function as dynamic nano-optical antennas, with their resonance behaviour tunable by chemical redox reactions. These plasmons originate from the mobile polaronic charge carriers of a poly(3,4-ethylenedioxythiophene:sulfate) (PEDOT:Sulf) polymer network. We demonstrate complete and reversible switching of the optical response of the nanoantennas by chemical tuning of their redox state, which modulates the material permittivity between plasmonic and dielectric regimes via non-volatile changes in the mobile charge carrier density. Further research may study different conductive polymers and nanostructures and explore their use in various applications, such as dynamic meta-optics and reflective displays.

Unraveling the doping-related charge carrier scattering mechanisms in two-dimensional materials such as graphene is vital for limiting parasitic electrical conductivity losses in future electronic applications. While electric field doping is well understood, assessment of mobility and density as a function of chemical doping remained a challenge thus far. In this work, we investigate the effects of cyclically exposing epitaxial graphene to controlled inert gases and ambient humidity conditions, while measuring the Lorentz force-induced birefringence in graphene at Terahertz frequencies in magnetic fields. This technique, previously identified as the optical analogue of the electrical Hall effect, permits here measurement of charge carrier type, density, and mobility in epitaxial graphene on silicon-face silicon carbide. We observe a distinct, nearly linear relationship between mobility and electron charge density, similar to field-effect induced changes measured in electrical Hall bar devices previously. The observed doping process is completely reversible and independent of the type of inert gas exposure.

Our goal in this paper is to show that a careful analysis of recall accuracy within a serial reproduction chain can add to a detailed qualitative analysis of the reproductions within the chain. The texts we chose are based on newspaper reports concerning current events, which are far from being mundane: reports of tragic events, even traumatic events. The participants were 216 students who were randomly assigned to 54 four-person reproduction chains, 18 for each of three 160-word texts. The reproduction chain is highly dependent on the recall accuracy of the first generation (i.e., the first participant in the reproduction chain). Thus, we argue (and show) that there should be a qualitative difference between chains starting off with a high level of recall accuracy from those starting off with a low level of recall accuracy. Our data-analytic approach is based on trend analysis, which we argue is an apt quantitative, holistic, dynamic, process-oriented type of analysis that is required in such research.

Background: Repeated exposures to UVB of human keratinocytes lacking functional p16(INK-4a) and able to differentiate induce an alternative state of differentiation rather than stress-induced premature senescence., Methodology/principal Findings: A 2D-DIGE proteomic profiling of this alternative state of differentiation was performed herein at various times after the exposures to UVB. Sixty-nine differentially abundant protein species were identified by mass spectrometry, many of which are involved in keratinocyte differentiation and survival. Among these protein species was TRIpartite Motif Protein 29 (TRIM29). Increased abundance of TRIM29 following UVB exposures was validated by Western blot using specific antibody and was also further analysed by immunochemistry and by RT-PCR. TRIM29 was found very abundant in keratinocytes and reconstructed epidermis. Knocking down the expression of TRIM29 by short-hairpin RNA interference decreased the viability of keratinocytes after UVB exposure. The abundance of involucrin mRNA, a marker of late differentiation, increased concomitantly. In TRIM29-knocked down reconstructed epidermis, the presence of picnotic cells revealed cell injury. Increased abundance of TRIM29 was also observed upon exposure to DNA damaging agents and PKC activation. The UVB-induced increase of TRIM29 abundance was dependent on a PKC signaling pathway, likely PKCdelta., Conclusions/significance: These findings suggest that TRIM29 allows keratinocytes to enter a protective alternative differentiation process rather than die massively after stress.

Skin cancers and extrinsic aging are delayed consequences of cumulative UV radiation insults. Exposure of human keratinocytes to UVB has been previously shown to trigger premature senescence. In order to explore the involvement of the cyclin-dependent kinase inhibitor p16(INK-4a) in UVB-induced premature senescence, we developed an original model of repeated sublethal exposures of human keratinocytes deficient in p16(INK-4a). We did not observe any significant increase of senescence-associated beta-galactosidase activity positive cells following UVB exposure in this cell line in contrast to primary keratinocytes, suggesting a role for p16(INK-4a) in UVB-induced senescence. However, we detected sustained DNA damage, prolonged cell cycle arrest, and induction of markers of epidermal differentiation like involucrin and filaggrin as consequences of the repeated exposures. Keratinocytes exposed to the same dose of UVB in a single exposure died. Furthermore, the abundance of the keratins 6, 16 and 17 was increased in keratinocytes exposed repeatedly to UVB suggesting an alternative differentiation. This model allows the induction of a state of differentiation observed in vivo with differentiation uncoupled from premature senescence.

The brightness of type Ia supernovae, and their homogeneity as a class, makes them powerful tools in cosmology, yet little is known about the progenitor systems of these explosions. They are thought to arise when a white dwarf accretes matter from a companion star, is compressed and undergoes a thermonuclear explosion. Unless the companion star is another white dwarf (in which case it should be destroyed by the mass-transfer process itself), it should survive and show distinguishing properties. Tycho's supernova is one of only two type Ia supernovae observed in our Galaxy, and so provides an opportunity to address observationally the identification of the surviving companion. Here we report a survey of the central region of its remnant, around the position of the explosion, which excludes red giants as the mass donor of the exploding white dwarf. We found a type G0-G2 star, similar to our Sun in surface temperature and luminosity (but lower surface gravity), moving at more than three times the mean velocity of the stars at that distance, which appears to be the surviving companion of the supernova.

Background: Intratracheal instillation of bleomycin (Bleo) into rodents serves as a model for human lung fibrosis. Various mouse strains respond differently to Bleo, and BALB/c mice are relatively resistant., Objective: Since T lymphocytes have been shown to play a major role in this model, the effect of the immunomodulator cyclosporin A (CyA) on lung fibrosis was studied in Bleo-'resistant' BALB/c mice., Methods: Pulmonary fibrosis was induced by a single intratracheal (IT) instillation of Bleo. One of the four following treatments was given to one of four groups of female BALB/c mice: (1) Bleo-CyA: IT Bleo and daily intraperitoneal (IP) injections of CyA 100 mg/day starting 1 day before IT instillation of Bleo; (2) Bleo-Sal: IT Bleo and IP injections of saline; (3) Sal-CyA: IT saline and IP CyA 100 mg/kg; (4) Sal-Sal: IT and IP saline. The animals were killed on day 14. Fibrosis was evaluated by analysis of hydroxyproline and by quantitative image analysis of the fibrosis fraction. Ex vivo IFN-gamma, IL-4, IL-13 and IL-5 secretion by peribronchial lymphatic tissue lymphocytes was measured., Results: Pretreatment with CyA upmodulated Bleo-induced lung fibrosis in the Bleo-'resistant' BALB/c mice; hydroxyproline was higher in Bleo-CyA compared to Bleo-Sal animals and both hydroxyproline and fibrosis fraction measurements were higher in Bleo-CyA compared to Sal-Sal. Cytokine secretion by lymphocytes demonstrated increased IFN-gamma/IL-4 and IFN-gamma/IL-13 mean secretion ratios in the Bleo-CyA animals compared to the Bleo-Sal animals., Conclusions: These results indicate that CyA upmodulates Bleo-induced lung fibrosis in Bleo-'resistant' BALB/c mice by allowing the emergence of a Th1 inflammatory response., (Copyright 2002 S. Karger AG, Basel)