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1.
Nature ; 620(7974): 516-520, 2023 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-37488359

RESUMEN

Terrestrial and sub-Neptune planets are expected to form in the inner (less than 10 AU) regions of protoplanetary disks1. Water plays a key role in their formation2-4, although it is yet unclear whether water molecules are formed in situ or transported from the outer disk5,6. So far Spitzer Space Telescope observations have only provided water luminosity upper limits for dust-depleted inner disks7, similar to PDS 70, the first system with direct confirmation of protoplanet presence8,9. Here we report JWST observations of PDS 70, a benchmark target to search for water in a disk hosting a large (approximately 54 AU) planet-carved gap separating an inner and outer disk10,11. Our findings show water in the inner disk of PDS 70. This implies that potential terrestrial planets forming therein have access to a water reservoir. The column densities of water vapour suggest in-situ formation via a reaction sequence involving O, H2 and/or OH, and survival through water self-shielding5. This is also supported by the presence of CO2 emission, another molecule sensitive to ultraviolet photodissociation. Dust shielding, and replenishment of both gas and small dust from the outer disk, may also play a role in sustaining the water reservoir12. Our observations also reveal a strong variability of the mid-infrared spectral energy distribution, pointing to a change of inner disk geometry.

2.
Faraday Discuss ; 245(0): 112-137, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37462069

RESUMEN

The understanding of planet formation has changed recently, embracing the new idea of pebble accretion. This means that the influx of pebbles from the outer regions of planet-forming disks to their inner zones could determine the composition of planets and their atmospheres. The solid and molecular components delivered to the planet-forming region can be best characterized by mid-infrared spectroscopy. With Spitzer low-resolution (R = 100, 600) spectroscopy, this approach was limited to the detection of abundant molecules, such as H2O, C2H2, HCN and CO2. This contribution will present the first results of the MINDS (MIRI mid-INfrared Disk Survey, PI:Th Henning) project. Due do the sensitivity and spectral resolution provided by the James Webb Space Telescope (JWST), we now have a unique tool to obtain the full inventory of chemistry in the inner disks of solar-type stars and brown dwarfs, including also less-abundant hydrocarbons and isotopologues. The Integral Field Unit (IFU) capabilities will enable at the same time spatial studies of the continuum and line emission in extended sources such as debris disks, the flying saucer and also the search for mid-IR signatures of forming planets in systems such as PDS 70. These JWST observations are complementary to ALMA and NOEMA observations of outer-disk chemistry; together these datasets will provide an integral view of the processes occurring during the planet-formation phase.

3.
HIV Med ; 22(2): 83-91, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32985122

RESUMEN

OBJECTIVES: Tenofovir disoproxil fumarate (TDF) is associated with reduced bone mineral density (BMD). We evaluated changes in BMD in women who switched from TDF, emtricitabine and a nonnucleoside reverse transcriptase inhibitor (TDF/FTC/NNRTI) to abacavir, lamivudine and dolutegravir (ABC/3TC/DTG). METHODS: We conducted a randomized controlled trial in which women aged ≥40 years were randomized 1:2 to continue TDF/FTC/NNRTI or switch to ABC/3TC/DTG. The primary endpoint was change in total hip BMD measured by dual-energy X-ray absorptiometry at week 48. Secondary endpoints were changes in BMD of the lumbar spine and femoral neck and markers of bone turnover and kidney function up to week 48. We conducted exploratory analyses of weight gain, insulin resistance and metabolic syndrome. Primary and secondary endpoints were analysed by linear regression, with multiple imputation for missing time points. RESULTS: In all, 91 women [mean age = 50.4 (standard deviation [SD] = 6.6) years, median CD4 cell count = 600 (interquartile range: 479-800) cells/µL] were randomized. Women who switched to ABC/3TC/DTG maintained viral suppression and experienced improvements in total hip BMD (mean adjusted difference = 1%, P = 0.027) and lumbar spine BMD (3%, P = 0.002), with no change in specific markers of bone turnover or renal tubular function. Although participants in the ABC/3TC/DTG arm gained more weight (1.8 kg, P = 0.046), the switch strategy was not associated with reduced insulin sensitivity or new-onset metabolic syndrome. CONCLUSIONS: Switching from TDF/FTC/NNRTI to ABC/3TC/DTG resulted in improved BMD. Although weight gain was common in women who switched from TDF/FTC/NNRTI to ABC/3TC/DTG, we did not detect adverse effects on glucose homeostasis. Larger studies need to confirm these findings.


Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Resistencia a la Insulina , Adulto , Fármacos Anti-VIH/uso terapéutico , Densidad Ósea , Didesoxinucleósidos/uso terapéutico , Emtricitabina/uso terapéutico , Femenino , Infecciones por VIH/tratamiento farmacológico , Compuestos Heterocíclicos con 3 Anillos , Humanos , Riñón , Lamivudine/uso terapéutico , Persona de Mediana Edad , Oxazinas , Piperazinas , Piridonas , Tenofovir/uso terapéutico , Aumento de Peso
4.
HIV Med ; 21(8): 536-540, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32544304

RESUMEN

The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.


Asunto(s)
Antirretrovirales/uso terapéutico , Betacoronavirus/efectos de los fármacos , Infecciones por Coronavirus/tratamiento farmacológico , Reposicionamiento de Medicamentos , Neumonía Viral/tratamiento farmacológico , Investigación/normas , COVID-19 , Infecciones por Coronavirus/prevención & control , Combinación de Medicamentos , Reposicionamiento de Medicamentos/normas , Reposicionamiento de Medicamentos/tendencias , Humanos , Hidroxicloroquina/uso terapéutico , Lopinavir/uso terapéutico , Pandemias/prevención & control , Neumonía Viral/prevención & control , Investigación/tendencias , Ritonavir/uso terapéutico , SARS-CoV-2 , Tenofovir/uso terapéutico , Factores de Tiempo
5.
HIV Med ; 21(9): 607-612, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33021067

RESUMEN

OBJECTIVES: The aim of the study was to analyse and compare estimated glomerular filtration rate (eGFR) slopes during exposure to tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) in individuals who initiated TAF, regardless of prior regimen, before October 2016. METHODS: An observational cohort study was conducted at 11 clinics in the UK and Ireland. Mixed effects models with random intercept and time terms fitted were used to generate and compare eGFR slopes while participants were exposed to TDF and TAF, with adjustment for age, eGFR at TDF/TAF initiation, gender, ethnicity, and time-updated CD4 cell count and HIV RNA measurements. RESULTS: Data were available for 357 subjects (median age 50 years; 80% male; 82% white/other ethnicity; 51% men who have sex with men; median nadir CD4 count 216 cells/µL). The median duration of exposure to TAF was 2.0 (interquartile range 1.6, 2.3) years. At TAF initiation, the median CD4 count was 557 cells/µL, the median eGFR was 80 mL/min/1.73 m2, and 86% had suppressed HIV infection. The mean adjusted eGFR slope during TDF and TAF exposure was -2.08 [95% confidence interval (CI) -2.24, -1.92] and 1.18 (95% CI 0.20, 1.52) mL/min/1.73 m2/year, respectively (P < 0.001). Individuals who experienced rapid eGFR decline (> 3 or 5 mL/min/1.73 m2/year) while receiving TDF experienced significant eGFR recovery while on TAF (P < 0.001). CONCLUSIONS: Significant improvement in eGFR slope was observed in patients who switched from TDF- to TAF-containing antiretroviral regimens. These data provide further support for the renal safety of TAF, and for switching those who experience progressive worsening of renal function from TDF to TAF.


Asunto(s)
Alanina/farmacología , Infecciones por VIH/tratamiento farmacológico , Riñón/fisiología , Tenofovir/análogos & derivados , Tenofovir/farmacología , Adulto , Alanina/uso terapéutico , Recuento de Linfocito CD4 , Estudios de Cohortes , Femenino , Tasa de Filtración Glomerular/efectos de los fármacos , Infecciones por VIH/fisiopatología , Humanos , Irlanda/etnología , Riñón/efectos de los fármacos , Masculino , Persona de Mediana Edad , Tenofovir/uso terapéutico , Resultado del Tratamiento , Reino Unido/etnología
6.
HIV Med ; 20(6): 377-391, 2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31034159

RESUMEN

OBJECTIVES: Reliable and timely HIV care cost estimates are important for policy option appraisals of HIV treatment and prevention strategies. As HIV clinical management and outcomes have changed, we aimed to update profiles of antiretroviral (ARV) usage pattern, patent/market exclusivity details and management costs in adults (≥ 18 years old) accessing HIV specialist care in England. METHODS: The data reported quarterly to the HIV and AIDS Reporting System in England was used to identify ARV usage pattern, and were combined with British National Formulary (BNF) prices, non-ARV care costs and patent/market exclusivity information to generate average survival-adjusted lifetime care costs. The cumulative budget impact from 2018 to the year in which all current ARVs were expected to lose market exclusivity was calculated for a hypothetical 85 000 (± 5000) person cohort, which provided an illustration of potential financial savings afforded by bioequivalent generic switches. Price scenarios explored BNF70 (September 2015) prices and generics at 10/20/30/50% of proprietary prices. The analyses took National Health Service (NHS) England's perspective (as the payer), and results are presented in 2016/2017 British pounds. RESULTS: By 2033, most currently available ARVs would lose market exclusivity; that is, generics could be available. Average per person lifetime HIV cost was ~£200 000 (3.5% annual discount) or ~£400 000 (undiscounted), reducing to ~£70 000 (3.5% annual discount; ~£120 000 undiscounted) with the use of generics (assuming that generics cost 10% of proprietary prices). The cumulative budget to cover 85 000 (± 5000) persons for 16 years (2018-2033) was £10.5 (± 0.6) billion, reducing to £3.6 (± 0.2) billion with the use of generics. CONCLUSIONS: HIV management costs are high but financial efficiency could be improved by optimizing generic use for treatment and prevention to mitigate the high cost of lifelong HIV treatment. Earlier implementation of generics as they become available offers the potential to maximize the scale of the financial savings.


Asunto(s)
Manejo de la Enfermedad , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Costos de la Atención en Salud/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Inglaterra , Femenino , Humanos , Masculino , Persona de Mediana Edad , Adulto Joven
7.
Vox Sang ; 113(4): 317-328, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29441601

RESUMEN

Conventional storage of platelet concentrates limits their shelf life to between 5 and 7 days due to the risk of bacterial proliferation and the development of the platelet storage lesion. Cold storage and cryopreservation of platelets may facilitate extension of the shelf life to weeks and years, and may also provide the benefit of being more haemostatically effective than conventionally stored platelets. Further, treatment of platelet concentrates with pathogen inactivation systems reduces bacterial contamination and provides a safeguard against the risk of emerging and re-emerging pathogens. While each of these alternative storage techniques is gaining traction individually, little work has been done to examine the effect of combining treatments in an effort to further improve product safety and minimize wastage. This review aims to discuss the benefits of alternative storage techniques and how they may be combined to alleviate the problems associated with conventional platelet storage.


Asunto(s)
Plaquetas/efectos de los fármacos , Conservación de la Sangre/métodos , Criopreservación/métodos , Refrigeración/métodos , Antiinfecciosos/farmacología , Conservación de la Sangre/efectos adversos , Humanos
8.
Nature ; 490(7418): 74-6, 2012 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-23038467

RESUMEN

Some planetary systems harbour debris disks containing planetesimals such as asteroids and comets. Collisions between such bodies produce small dust particles, the spectral features of which reveal their composition and, hence, that of their parent bodies. A measurement of the composition of olivine crystals (Mg(2-2x)Fe(2x)SiO(4)) has been done for the protoplanetary disk HD 100546 (refs 3, 4) and for olivine crystals in the warm inner parts of planetary systems. The latter compares well with the iron-rich olivine in asteroids (x ≈ 0.29). In the cold outskirts of the ß Pictoris system, an analogue to the young Solar System, olivine crystals were detected but their composition remained undetermined, leaving unknown how the composition of the bulk of Solar System cometary olivine grains compares with that of extrasolar comets. Here we report the detection of the 69-micrometre-wavelength band of olivine crystals in the spectrum of ß Pictoris. Because the disk is optically thin, we can associate the crystals with an extrasolar proto-Kuiper belt a distance of 15-45 astronomical units from the star (one astronomical unit is the Sun-Earth distance), determine their magnesium-rich composition (x = 0.01 ± 0.001) and show that they make up 3.6 ± 1.0 per cent of the total dust mass. These values are strikingly similar to those for the dust emitted by the most primitive comets in the Solar System, even though ß Pictoris is more massive and more luminous and has a different planetary system architecture.

9.
Psychol Health Med ; 23(10): 1168-1181, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29882424

RESUMEN

The aim of the current study was to use Structural Equation Modelling (SEM) to examine whether psychological flexibility (i.e. mindfulness, acceptance, valued-living) mediates the relationship between distress, irritable bowel syndrome (IBS) symptom frequency, and quality of life (QoL). Ninety-two individuals participated in the study (12 male, 80 female, Mage = 36.24) by completing an online survey including measures of visceral sensitivity, distress, IBS-related QoL, mindfulness, bowel symptoms, pain catastrophizing, acceptance, and valued-living. A final model with excellent fit was identified. Psychological distress significantly and directly predicted pain catastrophizing, valued-living, and IBS symptom frequency. Pain catastrophizing directly predicted visceral sensitivity and acceptance, while visceral sensitivity significantly and directly predicted IBS symptom frequency and QoL. Symptom frequency also had a direct and significant relationship with QoL. The current findings suggest that interventions designed to address unhelpful cognitive processes related to visceral sensitivity, pain catastrophizing, and psychological distress may be of most benefit to IBS-related QoL.


Asunto(s)
Catastrofización/psicología , Síndrome del Colon Irritable/psicología , Calidad de Vida/psicología , Estrés Psicológico/psicología , Dolor Visceral/psicología , Adulto , Ansiedad/psicología , Depresión/psicología , Femenino , Humanos , Síndrome del Colon Irritable/fisiopatología , Masculino , Persona de Mediana Edad , Atención Plena , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Dolor Visceral/fisiopatología , Adulto Joven
10.
HIV Med ; 17 Suppl 5: 3-16, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27714978

RESUMEN

In an era when most individuals with treated HIV infection can expect to live into old age, clinicians should proactively review their patients' current and future treatment needs and challenges. Clinical guidelines acknowledge that, in the setting of virological suppression, treatment switch may yield benefits in terms of tolerability, regimen simplification, adherence, convenience and long-term health considerations, particularly in the context of ageing. In this paper, we review evidence from six key clinical studies on switching virologically suppressed patients to regimens based on integrase strand transfer inhibitors (INSTIs), the antiretroviral class increasingly preferred as initial therapy in clinical guidelines. We review these studies and focus on the virological efficacy, safety, and tolerability of switching to INSTI-based regimens in suppressed HIV-positive individuals. We review the early switch studies SWITCHMRK and SPIRAL [assessing a switch from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL)-containing regimens], together with data from STRATEGY-PI [assessing a switch to elvitegravir (EVG)-containing regimens; EVG/cobicistat (COBI)/emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) vs. remaining on a PI/r-containing regimen], STRATEGY-NNRTI [assessing a switch to EVG/COBI/FTC/TDF vs. continuation of a nonnucleoside reverse transcriptase inhibitor (NNRTI) and two nucleoside reverse transcriptase inhibitors (NRTIs)], STRIIVING [assessing a switch to a dolutegravir (DTG)-containing regimen (abacavir (ABC)/lamivudine (3TC)/DTG) vs. staying on the background regimen], and GS study 109 [assessing a switch to EVG/COBI/FTC/tenofovir alafenamide fumarate (TAF) vs. continuation of FTC/TDF-based regimens]. Switching to INSTI-containing regimens has been shown to support good virological efficacy, with evidence from two studies demonstrating superior virological efficacy for a switch to EVG-containing regimens. In addition, switching to INSTI regimens was associated with improved tolerability and greater reported patient satisfaction and outcomes in some studies. INSTI-based regimens offer an important contemporary switch option that may be tailored to meet and optimize the needs of many patients.


Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/efectos de los fármacos , Respuesta Virológica Sostenida , Terapia Antirretroviral Altamente Activa/efectos adversos , Inhibidores de Integrasa VIH/efectos adversos , Humanos , Resultado del Tratamiento
11.
HIV Clin Trials ; 17(3): 123-30, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27125367

RESUMEN

BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 µmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.


Asunto(s)
Biomarcadores , Enfermedades Óseas/etiología , Enfermedades Cardiovasculares/etiología , Disfunción Cognitiva/etiología , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Hiperbilirrubinemia/etiología , Enfermedades Renales/etiología , Adulto , Terapia Antirretroviral Altamente Activa/efectos adversos , Densidad Ósea , Enfermedades Óseas/epidemiología , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Disfunción Cognitiva/epidemiología , Comorbilidad , Estudios Transversales , Femenino , Infecciones por VIH/tratamiento farmacológico , VIH-1 , Humanos , Hiperbilirrubinemia/epidemiología , Enfermedades Renales/epidemiología , Lípidos/sangre , Masculino , Persona de Mediana Edad , Inhibidores de Proteasas/administración & dosificación , Inhibidores de Proteasas/efectos adversos , Inhibidores de Proteasas/uso terapéutico , Factores de Riesgo
12.
Org Biomol Chem ; 14(48): 11371-11380, 2016 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-27805236

RESUMEN

We describe the qualitative and quantitative analysis of the complexation properties towards cations of a cyclic peptoid hexamer composed of alternating α- and ß-peptoid monomers, which bear exclusively chiral (S)-phenylethyl side chains (spe) that have no noticeable chelating properties. The binding of a series of monovalent and divalent cations was assessed by 1H NMR, circular dichroism, fluorescence and molecular modelling. In contrast to previous studies on cations binding by 18-membered α-cyclopeptoid hexamers, the 21-membered cyclopeptoid cP1 did not complex monovalent cations (Na+, K+, Ag+) but showed selectivity for divalent cations (Ca2+, Ba2+, Sr2+ and Mg2+). Hexacoordinated C-3 symmetrical complexes were demonstrated for divalent cations with ionic radii around 1 Å (Ca2+ and Ba2+), while 5-coordination is preferred for divalent cations with larger (Ba2+) or smaller ionic radii (Mg2+).


Asunto(s)
Peptoides/química , Cationes Bivalentes/química , Dicroismo Circular , Fluorescencia , Modelos Moleculares , Estructura Molecular , Espectroscopía de Protones por Resonancia Magnética
13.
J Phys Chem A ; 119(44): 10828-37, 2015 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-26447780

RESUMEN

Cationic cobalt clusters complexed with water Con(+)-H2O (n = 6-20) are produced through laser ablation and investigated via infrared multiple photon dissociation (IR-MPD) spectroscopy in the 200-1700 cm(-1) spectral range. All spectra exhibit a resonance close to the 1595 cm(-1) frequency of the free water bending vibration, indicating that the water molecule remains intact upon adsorption. For n = 6, the frequency of this band is blue-shifted, but it gradually converges to the free water value with increasing cluster size. In the lower-frequency range (200-650 cm(-1)) the spectra contain several bands which show a very regular frequency evolution, suggesting that the exact cluster geometry has little effect on the water-surface interaction. Density functional theory (DFT) calculations are carried out at the OPBE/TZP level for three representative sizes (n = 6, 9, 13) and indicate that the vibrations responsible for the resonances correspond to bending and torsional modes between the cluster and water moieties. The potential energy surfaces describing these interactions are very shallow, making the calculated harmonic frequencies and IR intensities very sensitive to small geometrical perturbations. We conclude that harmonic frequency calculations on (local) minima structures provide insufficient information for these types of cluster complexes and need to be complemented with calculations that provide a more extensive sampling of the potential energy surface.

14.
BMJ Open ; 14(1): e080250, 2024 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-38216201

RESUMEN

OBJECTIVE: To understand the experiences and perceptions of sexual health professionals responding to the May 2022 mpox outbreak in the UK. DESIGN: Cross-sectional, anonymous, online survey collecting quantitative and qualitative data. Convenience sample recruited via an international network of sexual health and HIV clinicians responding to mpox and promoted through clinical associations and social media. Survey domains included: clinical workload; preparedness, support, and training; safety at work; vaccination; and well-being. Qualitative descriptive analysis of open-text responses was conducted to support interpretation of the quantitative data. PARTICIPANTS: Participants who were employed as sexual health professionals in the UK and had direct clinical experience of mpox were included in the analysis. The survey was completed between 11 August and 31 October 2022 by 139 respondents, the majority of whom were doctors (72.7%), cis-female (70.5%) and White (78.4%). RESULTS: 70.3% reported that they were required to respond to mpox in addition to their existing clinical responsibilities, with 46.8% working longer hours as a result. In the open-text data, respondents highlighted that workload pressures were exacerbated by a lack of additional funding for mpox, pre-existing pressures on sexual health services, and unrealistic expectations around capacity. 67.6% of respondents reported experiencing negative emotional impact due to their mpox work, with stress (59.0%), fatigue (43.2%) and anxiety (36.0%) being the most common symptoms. 35.8% stated that they were less likely to remain in their profession because of their experiences during the mpox outbreak. In the open-text data, these feelings were ascribed to post-COVID exhaustion, understaffing and frustration among some participants at the handling of the mpox response. CONCLUSIONS: These findings indicate that sexual health services require increased funding and resources, along with evidence-based well-being interventions, to support sexual health professionals' outbreak preparedness and recovery.


Asunto(s)
Mpox , Salud Sexual , Humanos , Femenino , Estudios Transversales , Brotes de Enfermedades , Reino Unido/epidemiología
15.
Science ; 384(6700): 1086-1090, 2024 Jun 07.
Artículo en Inglés | MEDLINE | ID: mdl-38843318

RESUMEN

Very-low-mass stars (those less than 0.3 solar masses) host orbiting terrestrial planets more frequently than other types of stars. The compositions of those planets are largely unknown but are expected to relate to the protoplanetary disk in which they form. We used James Webb Space Telescope mid-infrared spectroscopy to investigate the chemical composition of the planet-forming disk around ISO-ChaI 147, a 0.11-solar-mass star. The inner disk has a carbon-rich chemistry; we identified emission from 13 carbon-bearing molecules, including ethane and benzene. The high column densities of hydrocarbons indicate that the observations probe deep into the disk. The high carbon-to-oxygen ratio indicates radial transport of material within the disk, which we predict would affect the bulk composition of any planets forming in the disk.

16.
HIV Med ; 12(5): 289-98, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21054749

RESUMEN

OBJECTIVE: We investigated whether adverse responses to highly active antiretroviral therapy (HAART) associated with late HIV presentation are secondary to low CD4 cell count per se or other confounding factors. METHODS: A longitudinal analysis of the UK Collaborative HIV Cohort (CHIC) Study of individuals starting HAART in 1998-2007 was carried out, comparing late presenters (presenting/starting HAART at a CD4 count <200 cells/µL) with late starters (presenting at a CD4 count>350 cells/µL; starting HAART at a CD4 count<200 cells/µL), using 'ideal starters' (presenting at a CD4 count>350 cells/µL; starting HAART at a CD4 count of 200-350 cells/µL) as a comparator. Virological, immunological and clinical (new AIDS event/death) outcomes at 48 and 96 weeks were analysed, with the analysis being limited to those remaining on HAART for>3 months. RESULTS: A total of 4978 of 9095 individuals starting first-line HAART with HIV RNA>500 HIV-1 RNA copies/mL were included in the analysis: 2741 late presenters, 947 late starters and 1290 ideal starters. Late presenters were more commonly female, heterosexual and Black African. Most started nonnucleoside reverse transcriptase inhibitors (NNRTIs); 48-week virological suppression was similar in late presenters and starters (and marginally lower than in ideal starters); by week 96 differences were reduced and nonsignificant. The median CD4 cell count increase in late presenters was significantly lower than that in late starters (weeks 48 and 96). During year 1, new clinical events were more frequent for late presenters [odds ratio (OR) 2.04; 95% confidence interval (CI) 1.19-3.51; P=0.01]; by year 2, event rates were similar in all groups. CONCLUSION: Amongst patients who initiate, and remain on, HAART, late presentation is associated with lower rates of virological suppression, blunted CD4 cell count increases and more clinical events compared with late starters in year 1, but similar clinical and immunological outcomes by year 2 to those of both late and ideal starters. Differences between late presenters and late starters suggest that factors other than CD4 cell count alone may be driving adverse treatment outcomes in late-presenting individuals.


Asunto(s)
Terapia Antirretroviral Altamente Activa , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto , Recuento de Linfocito CD4 , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Humanos , Estudios Longitudinales , Masculino , ARN Viral , Factores de Riesgo , Resultado del Tratamiento , Carga Viral
17.
J Exp Med ; 145(4): 948-67, 1977 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-192829

RESUMEN

6 of 20 cotton-top tamarins (Saguinus oedipus) inoculated with Epstein-Barr virus (EBV) developed diffuse malignant lymphoma resembling reticulum cell or immunoblastic sarcoma of man. Hyperplastic lymphoreticular lesions were induced in three additional animals; in two instances the hyperplastic lesions regressed. Inapparent infection with development of antibody occured in eight animals. In two animals there was no evidence of EBV infection. One animal died in the first week after inoculation of parasitic infection. 10 animals uninoculated or mock-inoculated developed neither lymphoproliferative disease nor antibody. The malignant lymphoma appeared to arise from a cell with an uncleaved vesicular nucleus found in the center of the germinal follicle. The prominent cytologic features of this cell were extensive formation or rough endoplasmic reticulum and elaboration of the cytoplasmic membrane with microvilli. Cell lines derived from these tumors did not have receptors for complement. IgFc, or sheep erythrocytes, and the cell lines adhered to glass and plastic. EB nuclear antigen was found in imprints of two lymph nodes, one with lymphoma and one with hyperplasia. EB virus DNA was detected directly in the tumors of three animals and in cell lines from two lymphomas. Typical herpes virus particles were found in supernatant fluids from cell lines obtained from lymph nodes with tumors and hyperplasia, as well as in lines derived from blood leukocytes of marmosets with inapparent infection. These virus preparations had the biologic property characteristic of EBV, namely, stimulation of cellular DNA synthesis and immortalization of human lymphocytes. The virus derived from two cell lines was neutralized by reference human sera with EBV antibody and not by antibody-negative human sera. The virus derived from the experimental lesions is thus indistinghishable from human EBV. The marmoset has enhanced susceptibility to oncogenesis by EB virus. Among identified factors which may play a role in the heightened tumorigenicity of EB virus in this species are the increased production of virus by transformed cells and the absence of membrane receptors for complement or IgFc on transformed cells.


Asunto(s)
Herpesvirus Humano 4 , Linfoma/etiología , Animales , Anticuerpos Antivirales/biosíntesis , Callitrichinae , Cápside/inmunología , Línea Celular , Núcleo Celular/ultraestructura , ADN Viral/análisis , Herpesvirus Humano 4/inmunología , Ganglios Linfáticos/patología , Linfoma/inmunología , Linfoma/patología , Mitosis , Pruebas de Neutralización
18.
Nature ; 432(7016): 479-82, 2004 Nov 25.
Artículo en Inglés | MEDLINE | ID: mdl-15565147

RESUMEN

Our Solar System was formed from a cloud of gas and dust. Most of the dust mass is contained in amorphous silicates, yet crystalline silicates are abundant throughout the Solar System, reflecting the thermal and chemical alteration of solids during planet formation. (Even primitive bodies such as comets contain crystalline silicates.) Little is known about the evolution of the dust that forms Earth-like planets. Here we report spatially resolved detections and compositional analyses of these building blocks in the innermost two astronomical units of three proto-planetary disks. We find the dust in these regions to be highly crystallized, more so than any other dust observed in young stars until now. In addition, the outer region of one star has equal amounts of pyroxene and olivine, whereas the inner regions are dominated by olivine. The spectral shape of the inner-disk spectra shows surprising similarity with Solar System comets. Radial-mixing models naturally explain this resemblance as well as the gradient in chemical composition. Our observations imply that silicates crystallize before any terrestrial planets are formed, consistent with the composition of meteorites in the Solar System.

19.
Nature ; 429(6987): 47-9, 2004 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-15129274

RESUMEN

Active galactic nuclei (AGNs) display many energetic phenomena--broad emission lines, X-rays, relativistic jets, radio lobes--originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN.

20.
Eur J Pharm Biopharm ; 154: 270-282, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-32717386

RESUMEN

This study reports the use of ITC in understanding the thermodynamics occurring for a controlled release system in which complexation has been exploited. In this study, a model drug, propranolol hydrochloride (PPN) was complexed with magnesium aluminium silicate (MAS) and these complexes were used in combination with polyethylene oxide (PEO) as a hydrophilic carrier at various concentrations to sustain the release of PPN. DSC, XRPD, ATR-FTIR and SEM/EDX were successfully used in characterising the produced complexes. 2D- SAXS data patterns for MAS and the produced complexes were shown to be symmetric and circular with the particles showing no preferred orientation at the nanometre scale. ITC studies showed differences between PPN adsorption onto MAS compared with PPN adsorption onto a MAS-PEO mixture. At both temperatures studied the binding affinity Ka was greater for the titration of PPN into the MAS-PEO mixture (5.37E + 04 ± 7.54E + 03 M at 25 °C and 8.63E + 04 ± 6.11E + 03 M at 37 °C), compared to the affinity obtained upon binding between PPN and MAS as previously reported suggesting a stronger binding with implications for the dissolution process. MAS-PPN complexes with the PEO polymer compacts displayed desired manufacturing and formulation properties for a formulator including, reduced plastic recovery therefore potentially reducing the risk of cracking/splitting and on tooling wear, controlled release of PPN at a significantly low (5%) polymer level as well as a zero-order release profile (case II transport) using up to 50% polymer level.


Asunto(s)
Compuestos de Aluminio/análisis , Liberación de Fármacos , Compuestos de Magnesio/análisis , Nanocompuestos/análisis , Polímeros/análisis , Dispersión del Ángulo Pequeño , Silicatos/análisis , Compuestos de Aluminio/metabolismo , Compuestos de Magnesio/metabolismo , Polímeros/metabolismo , Silicatos/metabolismo , Espectroscopía Infrarroja por Transformada de Fourier/métodos
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