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Abstract The formation of water ice clouds or hazes on Mars imposes substantial limitations on the vertical transport of water into the middle-upper atmosphere, impacting the planet’s hydrogen loss. Recent observations made by the Mars Environmental Dynamics Analyzer instrument onboard Mars 2020 Perseverance rover have shown a marked decline in water ice abundance within the mesosphere (above 35-40 km) when Mars is near its aphelion (near the northern summer solstice), notably occurring during solar longitudes (Ls) between Ls 70∘ and 80∘. Orbital observations around the same latitudes indicate that temperatures between ~ 30-40 km reach a minimum during the same period. Using cloud microphysics simulations, we demonstrate that this decrease in temperature effectively increases the amount of water cold-trapped at those altitudes, confining water ice condensation to lower altitudes. Similarly, the reinforcement of the cold trap induced by the lower temperatures results in significant reductions in the water vapor mixing ratio above 35–40 km, explaining the confinement of water vapor observed around aphelion from orbiters.

Introduction Colonocyte oxidation of bacterial-derived butyrate has been reported to maintain synergistic obligate anaerobe populations by reducing colonocyte oxygen levels; however, it is not known whether this process is disrupted during the progression of type 2 diabetes. Our aim was to determine whether diabetes influences colonocyte oxygen levels in the University of California Davis type 2 diabetes mellitus (UCD-T2DM) rat model.Research design and methods Age-matched male UCD-T2DM rats (174±4 days) prior to the onset of diabetes (PD, n=15), within 1 month post-onset (RD, n=12), and 3 months post-onset (D3M, n=12) were included in this study. Rats were administered an intraperitoneal injection of pimonidazole (60 mg/kg body weight) 1 hour prior to euthanasia and tissue collection to estimate colonic oxygen levels. Colon tissue was fixed in 10% formalin, embedded in paraffin, and processed for immunohistochemical detection of pimonidazole. The colonic microbiome was assessed by 16S gene rRNA amplicon sequencing and content of short-chain fatty acids was measured by liquid chromatography-mass spectrometry.Results HbA1c % increased linearly across the PD (5.9±0.1), RD (7.6±0.4), and D3M (11.5±0.6) groups, confirming the progression of diabetes in this cohort. D3M rats had a 2.5% increase in known facultative anaerobes, Escherichia–Shigella, and Streptococcus (false discovery rate

Abstract Background Clostridioides difficile infections have become more frequently diagnosed and associated with greater disease severity, which has resulted in an increase burden on the healthcare system. These increases are attributed to the increased prevalence of hypervirulent strains encompassing select ribotypes. These epidemic ribotypes were characterized as hypervirulent due to higher in vitro spore and toxin production, as well as increased incidence, severity and mortality within patients. However, it is unclear whether epidemic ribotypes are truly more virulent than non-epidemic ribotypes in vivo. Furthermore, there is conflicting evidence about the ability of a strain’s in vitro phenotype to be predictive of their in vivo virulence. The goals of the current studies were to determine if epidemic ribotypes are more virulent than other ribotypes in animal models, and whether the in vitro virulence phenotype of an isolate or ribotype predict in vivo virulence. Results To determine if epidemic strains were truly more virulent than other non-epidemic strains, the in vivo virulence of 13 C. difficile isolates (7 non-epidemic and 6 epidemic ribotype isolates) were determined in murine and hamster models of CDI. The isolates of epidemic ribotype of C. difficile were found to be more virulent in both the murine and hamster models than non-epidemic isolates. In particular, the group of epidemic ribotypes of C. difficile had lower LD50 values in hamsters. The increased severity of disease was associated with higher levels of Toxin A and Toxin B production found in fecal samples, but not numbers of organisms recovered. The isolates were further characterized for their in vitro virulence phenotypes, e.g. toxin production, growth rates, spore formation and adherence of spores to intestinal epithelial cell lines. Although there were higher levels of toxins produced and greater adherence for the group of epidemic ribotypes, the in vitro profiles of individual isolates were not always predictive of their in vivo virulence. Conclusions Overall, the group of epidemic ribotypes of C. difficile were more virulent in vivo despite individual isolates having similar phenotypes to the non-epidemic isolates in vitro.

Native Hawaiians are proud and resilient people who have endured significant impacts from colonization. Despite being in a time of vibrant cultural revitalization, Native Hawaiians have a shorter life expectancy than other racial and ethnic groups in Hawai‘i. The primary aim of this paper was to share data from the first year of a 5-year study with Native Hawaiian kūpuna (elders) on their experiences with healthcare, along with barriers to accessing healthcare. Ten kūpuna living in rural areas of Hawai‘i participated in three interviews each, which were held in an informal, talk-story style. The first interview focused on establishing rapport. The second interview focused on the kūpuna's strengths, resiliencies, and what they would like to pass to the next generation. The third interview focused on the elders' experiences with healthcare, which is the focus of this paper. All ten kūpuna reported growing up with limited access to Western healthcare; rather, their families successfully treated many illnesses and injuries with lā‘au lapa‘au (Hawaiian herbal medicine) and other traditional healing practices, as they had done for generations. As Western medicine became more prevalent and accessible, they used both, but many preferred holistic treatments such as prayer, a return to the traditional diet, and lā‘au lapa‘au. As a group, the kūpuna rated their health as fair to good; two had diabetes, two had cardiovascular disease, four had neuropathies, and five were cancer survivors. The kūpuna reported high turnover among providers in rural communities. Limited access to specialists often required them to travel to Honolulu for care, which was costly and especially difficult during coronavirus disease 2019 (COVID-19). Regardless of provider ethnicity, the kūpuna appreciated those who took the time to get to know them as people and respected Hawaiian cultural practices. They advised that Western providers speak honestly and directly, have compassion, and build connections to patients and their communities.

In the first 600 sols of the Mars2020 mission, L _S 5.6 ^o – 316.8 ^o , 46 cloud movies and 145 cloud surveys were collected to observe clouds at Jezero Crater, the landing site of the Perseverance Rover. Cloud movies were processed using the Mean-Frame Subtraction (MFS) method for revealing cloud structures, which were subsequently analyzed using digital-image processing. Two-dimensional Fast Fourier Transforms (2D-FFT) were used to compute cloud structure sizes ranging from 2.90 to 15.25 km for clouds between 30 and 50 km altitude, based on coincident Mars Climate Sounder vertical profiles of atmospheric water-ice. Same-value thresholding was used to detect the cloud structures in MFS-processed and projected cloud movies. The resolution dependence that was needed to resolve these structures over various thresholds was examined to find multifractal scaling of Mars clouds for resolutions between 0.1 and 1.6 km. We characterize the multiscaling observed in the images and its implications for the design of cloud-tracking cameras from the surface as well as for cloud-resolving models.

La sociedad civil organizada cumple un rol cada vez más relevante en el mundo y Chile no es la excepción: discusiones públicas y reformas en distintos ámbitos han sido protagonizadas por movimientos y organizaciones cívicas. Sin embargo, la intersección entre las comunicaciones y la sociedad civil es un campo aún poco explorado en el país. Este artículo presenta los resultados de un estudio exploratorio sobre los desafíos que enfrentan quienes desempeñan labores de comunicaciones en organizaciones del tercer sector. Para esto, se realizaron dos grupos focales, en los cuales, 15 directores y profesionales de comunicaciones de distintas organizaciones de la sociedad civil en Chile describieron la situación actual y los desafíos que visualizan en el ejercicio de sus labores. Varios de los hallazgos coinciden con los descritos en la literatura internacional, pero surgen tres elementos distintivos de la experiencia nacional: la dependencia de los medios tradicionales, la falta de herramientas y recursos para afrontar los impactos de la transformación digital de las comunicaciones y la escasa valoración del aporte de los comunicadores a sus organizaciones.

Le poème épique de William Blake, Milton, commence par une diatribe contre les mercenaires, ce qui, dans le contexte miltonien, fait immédiatement penser aux Considerations Touching the Likeliest Means to Remove Hirelings out of the Church. Ces deux textes font référence aux discours bibliques sur le travail, plus particulièrement aux notions chrétiennes de vocation et de travail et à la distinction qu’établit Jésus entre le bon berger et le mercenaire dans la parabole du berger (Jean 10.1-21). Pour Milton et Blake, ce discours sur le travail eut une influence directe sur leur conception de ce qu’est l’artiste, le public et de leurs responsabilités et rôles mutuels. Dans son poème, Blake prend comme point de départ la distinction biblique de Milton entre le vrai travailleur et le mercenaire, et fait de cette distinction le fondement de l’énigmatique Chant du Barde qui déclenche l’action du poème. Le Chant du Barde est, entre autres, une parabole concernant le travail qui rejoint la plupart des préoccupations exprimées dans la Bible ou développées par Milton. En fait, la forme et le contenu paraboliques du Chant du Barde deviennent des moyens essentiels pour, à la fois, accomplir et décrire le genre de travail que Blake considérait comme la mission du vrai travailleur et du vrai poète-prophète.

As with most health care provider education programs, physical therapy programs seek ways to develop professional behaviors of students. This study describes the integration of a one-week service-learning experience into an existing clinical internship. Quantitative and qualitative data were analyzed between groups of students who participated in the experience, expressed a desire to participate but were unable to, and those who did not wish to participate. Results suggest that engaging in, as well as the desire to engage in, a service-learning project for under-served members of our community is associated with professional behavior development from students’ and clinical preceptors’ perspectives.

The molecular determinants of the immune response to Mycobacterium tuberculosis HN878 infection in a rabbit model of pulmonary cavitary tuberculosis were studied. Aerosol infection of rabbits resulted in a highly differentially expressed global transcriptome in the lungs at 2 weeks, which dropped at 4 weeks and then gradually increased. While IFNγ was progressively upregulated throughout the infection, several other genes in the IFNγ network were not. T-cell activation network genes were gradually upregulated and maximally induced at 12 weeks. Similarly, the IL4 and B-cell activation networks were progressively upregulated, many reaching high levels between 12 and 16 weeks. Delayed peak expression of genes associated with macrophage activation and Th1 type immunity was noted. Although spleen CD4+ and CD8+ T cells showed maximal tuberculosis antigen-specific activation by 8 weeks, macrophage activation in lungs, lymph nodes and spleen did not peak until 12 weeks. In the lungs, infecting bacilli grew exponentially up to 4 weeks, followed by a steady-state high bacillary load to 12 weeks that moderately increased during cavitation at 16 weeks. Thus, the outcome of HN878 infection of rabbits was determined early during infection by a suboptimal activation of innate immunity and delayed T-cell activation.

Mycoplasma lipoproteins are recognized by Toll-like receptors (TLR), but TLRs' role in responses to infection are unknown. Mycoplasma pulmonis is a naturally occurring respiratory pathogen in mice. In the current study, we used TLR-transfected HEK cells and TLR2(-/-) bone marrow-derived dendritic cells to demonstrate TLR2-mediated events are important in the initial host-mycoplasma interactions promoting cytokine responses. As we found alveolar macrophages expressed TLR1, TLR2 and TLR6 mRNAs, a role for TLR2 in innate immune clearance in lungs was examined. Three days post-infection, TLR2(-/-) mice had higher M. pulmonis numbers in lungs, but not in nasal passages. However, TLR2(-/-) mice had higher lung cytokine levels, indicating TLR2-independent mechanisms are also involved in host responses. Thus, TLR2 plays a critical role in the ability of innate immunity to determine M. pulmonis numbers in the lung, and it is likely that early after respiratory infection that TLR2 recognition of M. pulmonis triggers initial cytokine responses of host cells.

Background: Prostate cancer (PCa) is the most common cancer in men in the UK. Patients with intermediate-risk, clinically localised disease are offered radical treatments such as surgery or radiotherapy, which can result in severe side effects. A number of alternative partial ablation (PA) technologies that may reduce treatment burden are available; however the comparative effectiveness of these techniques has never been evaluated in a randomised controlled trial (RCT)., Objectives: To assess the feasibility of a RCT of PA using high-intensity focused ultrasound (HIFU) versus radical prostatectomy (RP) for intermediate-risk PCa and to test and optimise methods of data capture., Design: We carried out a prospective, multicentre, open-label feasibility study to inform the design and conduct of a future RCT, involving a QuinteT Recruitment Intervention (QRI) to understand barriers to participation., Setting: Five NHS hospitals in England., Participants: Men with unilateral, intermediate-risk, clinically localised PCa., Interventions: Radical prostatectomy compared with HIFU., Primary Outcome Measure: The randomisation of 80 men., Secondary Outcome Measures: Findings of the QRI and assessment of data capture methods., Results: Eighty-seven patients consented to participate by 31 March 2017 and 82 men were randomised by 4 May 2017 (41 men to the RP arm and 41 to the HIFU arm). The QRI was conducted in two iterative phases: phase I identified a number of barriers to recruitment, including organisational challenges, lack of recruiter equipoise and difficulties communicating with patients about the study, and phase II comprised the development and delivery of tailored strategies to optimise recruitment, including group training, individual feedback and 'tips' documents. At the time of data extraction, on 10 October 2017, treatment data were available for 71 patients. Patient characteristics were similar at baseline and the rate of return of all clinical case report forms (CRFs) was 95%; the return rate of the patient-reported outcome measures (PROMs) questionnaire pack was 90.5%. Centres with specific long-standing expertise in offering HIFU as a routine NHS treatment option had lower recruitment rates (Basingstoke and Southampton) - with University College Hospital failing to enrol any participants - than centres offering HIFU in the trial context only., Conclusions: Randomisation of men to a RCT comparing PA with radical treatments of the prostate is feasible. The QRI provided insights into the complexities of recruiting to this surgical trial and has highlighted a number of key lessons that are likely to be important if the study progresses to a main trial. A full RCT comparing clinical effectiveness, cost-effectiveness and quality-of-life outcomes between radical treatments and PA is now warranted., Future Work: Men recruited to the feasibility study will be followed up for 36 months in accordance with the protocol. We will design a full RCT, taking into account the lessons learnt from this study. CRFs will be streamlined, and the length and frequency of PROMs and resource use diaries will be reviewed to reduce the burden on patients and research nurses and to optimise data completeness., Trial Registration: Current Controlled Trials ISRCTN99760303., Funding: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 22, No. 52. See the NIHR Journals Library website for further project information., Competing Interests: Ray Fitzpatrick is a member of the Health Technology Assessment Priority Research Advisory Methods Group. Richard Hindley has received payments for lecturing and proctoring for SonaCare Medical (Charlotte, NC, USA; high-intensity focused ultrasound treatment). Hashim U Ahmed reports grants and personal fees from SonaCare Medical and grants from Trod Medical (Heverlee, Belgium) and Sophiris Bio Inc. (La Jolla, CA, USA) outside the submitted work.

The aim of this study was to investigate in human skin in vivo the role of nitric oxide in maintaining resting vascular tone, in the vasodilatation caused by local warming and by ultraviolet B light exposure, and in the response to exogenous calcitonin gene-related peptide (CGRP). Cutaneous blood flow was assessed by planimetry of the visible erythema or pallor and by laser Doppler flowmetry. Intradermal injection of the inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester (L-NAME; 25 nmol), into forearm skin produced a visible pallor and a reduction of blood flow at a controlled ambient temperature of 21 degrees C. The control, NG-nitro-D-arginine methyl ester (D-NAME; 25 nmol) or NG-monomethyl-L-arginine (L-NMMA; 25 nmol) did not cause pallor or reduce blood flow. L-NAME and L-NMMA caused dose- and time-dependent increases in pallor, and reductions in cutaneous blood flow in skin that had been locally warmed by immersion in water at 45 degrees C and in skin that had been exposed to ultraviolet B light. D-NAME and D-NMMA at comparable concentrations did not have the effects on skin blood flow observed with the L forms. L-NAME and L-NMMA both inhibited the increased blood flow in human skin caused by the intradermal injection of CGRP (12.5 or 25 pmol). The reduction of CGRP-induced increase of blood flow by L-NAME was reversed by L-arginine. Neither D-NAME nor D-NMMA inhibited the increase in blood flow caused by CGRP. Neither L-NAME nor L-NMMA inhibited the increase in blood flow in human skin caused by the intradermal injection of prostaglandin E2 (63 pmol). The data show that nitric oxide is involved in the maintenance of resting blood flow in human skin and also in the cutaneous vasodilator responses to local warming, ultraviolet B irradiation, or injection of CGRP.

Vibration white finger or hand-arm vibration syndrome is the episodic blanching of the fingers in response to cold occurring in those who work with hand held vibrating tools. Clinically the condition differs from primary Raynaud's phenomenon as persistent paraesthesiae and pain are common in the hands and arms and these occur independently from the 'white attacks'. Symptoms can become severe enough to warrant a change of occupation. Industrial compensation may be awarded for vibration white finger but, at present, no simple or reliable objective diagnostic test is available. Calcitonin gene-related peptide (CGRP) is a neuropeptide with powerful vasodilator properties. A deficiency of immunoreactive CGRP nerve fibres has been previously demonstrated in the digital cutaneous microvasculature of patients with primary and secondary Raynaud's phenomenon with the distribution and quantity of other types of nerve fibres not being significantly altered. To determine if the innervation of the cutaneous microvasculature in vibration white finger was also abnormal skin biopsy samples from the fingers of 15 patients with vibration white finger, six healthy age matched controls who worked with vibrating machinery and 26 healthy age matched controls who were heavy manual workers without exposure to vibrating machinery were examined by immunohistochemistry. To try to correlate any histological abnormalities with clinical neurological deficit sensory nerve conduction studies have so far been performed in six patients with vibration white finger.(ABSTRACT TRUNCATED AT 250 WORDS)